gebhart/patrepeval huggingface dataset:
Quantitative analysis of the endocytic system involved in hormone-induced receptor internalization. (1990)

We have developed a quantitative method to evaluate the interaction between cell surface receptors and the endocytic apparatus. This method exploits occupancy-dependent changes in internalization rates that occur in cells expressing high numbers of receptors. We found that constitutive internalization of the transferrin receptor behaves as a simple, first order process that is unaltered by ligand. Internalization of the epidermal growth factor (EGF) receptor, however, behaves as a saturable, second order process that is induced by receptor occupancy. Internalization of EGF receptors occurs through at least two distinct pathways: a low capacity pathway that has a relatively high affinity for occupied receptors, and a low affinity pathway that has a much higher capacity. The high affinity pathway was observed in all cells having receptors with intrinsic tyrosine kinase activity. Mutant EGF receptors lacking kinase activity could not utilize the high affinity pathway and were internalized only through the low affinity one. Mutated receptors with decreased affinity for kinase substrates were also internalized at decreased rates through the high affinity, inducible pathway. In the case of vitellogenin receptors in Xenopus oocytes, occupied receptors competed more efficiently for internalization than empty ones. Insulin increased the endocytic capacity of oocytes for vitellogenin receptors. Similarly, serum increased the capacity of the inducible pathway for EGF receptors in mammalian cells. These data are consistent with a model of internalization in which occupied receptors bind to specific cellular components that mediate rapid internalization. Ligand-induced internalization results from an increase in the affinity of occupied receptors for the endocytic apparatus. Hormones can also indirectly regulate endocytosis by increasing the number of coated pits or their rate of internalization. The ability to dissect receptor-specific effects from cell-specific ones should be very useful in investigating the molecular mechanisms of receptor mediated endocytosis.
Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy (2005)

MAGE genes are silent in normal tissues except testis but are expressed in a variety of neoplastic lesions, and therefore represent ideal targets for immunotherapy. We analysed the expression of 6 MAGE-A genes (MAGE-A1 to -A6) to determine potential implications of these antigens as targets for immunotherapy in oral squamous cell carcinoma (OSCC). Oral tumor specimens (n=21) and non-neoplastic tissue samples (n=10) of oral mucosa from healthy patients were examined by a highly sensitive reverse transcription-nested polymerase chain reaction (MAGE-1- to -6 assay) which detect any cancer cells that express at least one of six MAGE subtype genes and allows also the identification of individual MAGE isotypes (M1 to M6). MAGE expression was restricted to neoplastic specimens. No expression of MAGE was observed in the non-neoplastic normal oral mucosal tissues. Fifteen of 21 (71%) oral carcinomas expressed at least one of MAGE-A1 to -6. The expression pattern of subtypes was heterogeneous: 62% of the tumor patients were positive for MAGE-3, 57% for MAGE-4, 48% for MAGE-6, 43% for MAGE-1, 38% for MAGE-2 and 24% for MAGE-5. Also coexpression of the genes could be determined: 13 (62%) coexpressed two, 10 (48%) coexpressed three, 8 (38%) coexpressed four, 6 (29%) coexpressed five and 5 coexpressed six of the 6 subtypes tested. The high incidence of MAGE expression in oral cancer indicates that monitoring of MAGE-A subtype expression in OSCC may be of potential interest to determine new immunotherapeutic targets and may be a possibility of specific immunotherapy with polyvalent anti-genes for this disease.
Pyrromethene‐BF2 complexes (4,4′‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacenes). Synthesis and luminescence properties (1977)

Abstract BF 2 complexes of alkylated pyrromethenes were prepared by reacting the corresponding pyrromethenes with BF 3 ·OEt 2 under basic conditions. A striking aspect of these complexes is a pronounced fluorescence in organic solvents, even at room temperature, with fluorescence quantum yields between 0.3‐0.8. The efficiency and wavelength maximum of the fluorescence seems to be correlated with the substitution pattern at the 2 and 6 position. In none of these systems could phosphorescence be detected.
Symbols for Amino-Acid Derivatives and Peptides (1972)

Rules for Abbreviations and Symbols of Chemical Names of Special Interest in Biological Chemistry"(2)).They sought to reconcile the needs of the protein chemist, i.e. indication of amino-acid sequences, with those of persons concerned more with the chemical reactions of proteins and the synthesis of polypeptides, i.e. the need for conveying more detailed chemical information in abbreviated form.Recent progress in the field of peptide synthesis and in the chemical modification of proteins has made necessary a revision of these "Tentative Rules.
A Life Course Approach to Women's Health (2002)

Abstract How far is the health of middle-aged and older women shaped by biological, social, and psychological processes that begin in pre-natal development, childhood, adolescence, or early adult life? Do health risks gradually accumulate over the life course or do experiences as a child and young adult have interactive effects on health in midlife and beyond? Are women now reaching middle age in better health than those from previous generations? This book reviews the latest scientific evidence on biological and social factors at each stage of life that have long-term effects on reproductive outcomes, breast cancer, cardiovascular disease, diabetes, musculoskeletal ageing, depression, body weight, and body dissatisfaction. There is growing evidence that the sources of risk to physical and mental health occur across the course of life, not just in adult life, and in some instances reach right back to pre-natal development, or the previous generation. Contributors in this book draw on their varied expertise in epidemiology, endocrinology, physiology, developmental psychology, sociology, and anthropology to identify the pathways that link early life experiences, reproductive events, adult lifestyle and lifetime socio-economic circumstances to later health. This book looks for connections between development and ageing, and between the childhood and adult social environment.
Catalytic Formation of Cyclic Carbonates from Epoxides and CO2 with Chromium Metalloporphyrinates (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalytic Formation of Cyclic Carbonates from Epoxides and CO2 with Chromium MetalloporphyrinatesWilliam J. Kruper and David D. DellarCite this: J. Org. Chem. 1995, 60, 3, 725–727Publication Date (Print):February 1, 1995Publication History Published online1 May 2002Published inissue 1 February 1995https://pubs.acs.org/doi/10.1021/jo00108a042https://doi.org/10.1021/jo00108a042research-articleACS PublicationsRequest reuse permissionsArticle Views2263Altmetric-Citations275LEARN 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
Cloning and expression of PTP-PEST. A novel, human, nontransmembrane protein tyrosine phosphatase. (1993)

The polymerase chain reaction was used to amplify protein tyrosine phosphatase (PTPase)-related cDNA from a template of total RNA isolated from human skeletal muscle. A novel PTPase, which we term PTP-PEST, was detected by this method. The polymerase chain reaction fragment was used to screen two different HeLa cell libraries to obtain full length cDNA clones. The cDNA predicts a protein of 510 amino acids, approximately 60 kDa, that does not contain an obvious signal sequence or transmembrane segment suggesting it is a nonreceptor type enzyme. The PTPase domain is located in the N-terminal portion of the molecule and displays approximately 35% identity to other members of this family of enzymes. The C-terminal segment is rich in Pro, Glu, Asp, Ser, and Thr residues, possessing features of PEST motifs which have previously been identified in proteins with very short intracellular half-lives. The protein was expressed in Escherichia coli as a fusion product with glutathione S-transferase. Intrinsic activity was demonstrated in vitro against a variety of phosphotyrosine-containing substrates including BIRK, the autophosphorylated cytoplasmic kinase domain of the insulin receptor beta subunit. It did not dephosphorylate phosphoseryl-phosphorylase a. PTP-PEST mRNA is broadly distributed in a variety of cell lines. Stimulation of human rhabdomyosarcoma A204 cells, a transformed muscle line, with insulin led to an approximately 4-fold induction of PTP-PEST mRNA within 36 h.
Peptide immunization in humans: a combined CD8+/CD4+ T cell-targeted vaccine restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes (CTL) (1996)

Immunization with short antigenic peptides represents a potential strategy to induce peptide-specific CTL in vivo. In this study, a synthetic vaccine consisting of an HIV-derived, HLA-A2.1-binding CTL epitope and a tetanus toxin-derived T helper epitope was evaluated for its capacity to induce peptide-specific CTL in humans. Thirteen volunteers were immunized and boosted twice with 100 micrograms of the CTL epitope plus 300 micrograms of the T helper peptide (p30). Peripheral blood mononuclear cells (PBMC) were regularly analysed for cytotoxic and proliferative responses before, between and after the immunizations, and the serum was tested for anti-peptide antibodies. No unequivocal induction of HIV peptide-specific CTL in any of the volunteers was observed. However, a wide pattern of mild and transient side reactions was observed, ranging from local redness at the injection site to generalized exanthema, myalgias, arthralgias and fever. The side-effects were related to the T helper epitope, as they were similar to the side-effects experienced after tetanus immunization, correlated to the magnitude of the p30-specific in vitro proliferative response, and occurred only if p30 was co-injected. No antibodies against the HIV-derived peptides nor against p30 were detectable in the serum after repeated immunizations. The data suggest that the CTL peptide, at the concentration used in this study, failed to induce a cytotoxic immune response in vivo, although the T helper peptide seems to be capable of restimulating the specific memory T cells.
Affinity selection of a camelized V(H) domain antibody inhibitor of hepatitis C virus NS3 protease (1997)

The HCV genome encodes, within the NS3 gene, a serine protease whose activity specifically cleaves the viral polyprotein precursor. Proteolytic processing of HCV polyprotein precursor by the viral NS3 proteinase is essential for virion maturation and designing specific inhibitors of this protease as possible anti-viral agents is a desirable and practical objective. With a view to studying both the function of HCV NS3 protease and to designing inhibitors of this enzyme, we directed our interest towards engineering macromolecular inhibitors of the viral protease catalytic activity. We describe here the affinity-selection and biochemical characterization of one inhibitor, cV(H)E2, a 'camelized' variable domain antibody fragment, isolated from a phage displayed synthetic repertoire, which is a potent and selective inhibitor of proteolysis by the NS3 enzyme. In addition to being useful as a biological probe to study the function of HCV protease, this inhibitor can serve as a potential pharmacophore model to design antivirals. Moreover, the results suggest a way of engineering improved human-derived small recognition units tailored for enzyme inhibition.
Incorporation of Acetate, Propionate, and Methionine into Rapamycin by Streptomyces hygroscopicus (1991)

Labelling experiments with 13C-labelled precursors demonstrated that the majority of the macrolide ring of rapamycin is formed from six acetate and seven propionate units. A two-carbon unit in the ring was not labelled by acetate, propionate, glycine, or methionine. Methionine and glycine did, however, label the three methoxy groups of rapamycin to a high degree. Results from the incorporation experiments demonstrated that there were errors in the published 13C-nmr spectral assignments for rapamycin; these have now been corrected.
The use of 5′-Phosphate Derivatives of Nucleoside Analogues as Inhibitors of HIV-1 Replication (1995)

A series of phosphate esters of nucleoside analogues was synthesized and tested for anti-HIV activity in cell culture. A number of these compounds were potent inhibitors of HIV-replication with ED 50 ≥ 10 nM. The most potent compounds were phosphate esters of the most potent nucleosides, 3′-fluoro-3′-deoxythymidine (FLT) and 3′-azido-3′-deoxythymidine (AZT). In cell culture, the inhibition by one of these derivatives was shown to be reversed by thymidine. Also, the AZT analogue was less active against AZT-resistant virus. None of the compounds tested was directly inhibitory of HIV reverse transcriptase. The compounds were found to be labile; the rate of hydrolysis and the identity of the products varied depending on the substituents on the phosphorus atom. Activation of the most active analogue, FLT-5′-(methoxyglycinyl S-(N-methylcarbamoylmethyl))thiophosphate (JCA-304), involved a pH-dependent hydrolysis, which increased with increasing pH. The hydrolysis was not dependent on HIV proteinase, the presence of MT4 cells or enzymatic activity originating from the culture medium. The product of hydrolysis of JCA-304 was the free nucleoside (FLT); FLT-5′-monophosphate was not detected. The corresponding acyclovir analogue was not active against thymidine-kinase-deficient herpes simplex virus in Vero cells. Hydrolysis of FLT-5′-(S-(N-methylcarbamoylmethyl))thiophosphate (JCA-319) was observed in cell culture medium but not in buffer at the same pH. The product was identified as FLT-5′-monophosphate. Neither of these compounds was seen as an intermediate in the hydrolysis of JCA-304. The results suggest that the compounds are prodrugs activated by a non-enzymatic hydrolysis and a cytosolic phosphorylation yielding potent inhibitors of HIV reverse transcriptase. The cellular stability of substituted 5′-phosphate derivatives cannot be predicted from their behaviour in buffer or from the hydrolysis of closely related analogues.
Nanomaterial standards for efficacy and toxicity assessment (2009)

Decreased toxicity via selective delivery of cancer therapeutics to tumors has become a hallmark achievement of nanotechnology. In order to be optimally efficacious, a systemically administered nanomedicine must reach cancer cells in sufficient quantities to elicit a response and assume its active form within the tumor microenvironment (e.g., be taken up by cancer cells and release a toxic component once within the cytosol or nuclei). Most nanomedicines achieve selective tumor accumulation via the enhanced permeability and retention (EPR) effect or a combination of the EPR effect and active targeting to cellular receptors. Here, we review how the fundamental physicochemical properties of a nanomedicine (its size, charge, hydrophobicity, etc.) can dramatically affect its distribution to cancerous tissue, transport across vascular walls, and retention in tumors. We also discuss how nanoparticle characteristics such as stability in the blood and tumor, cleavability of covalently bound components, cancer cell uptake, and cytotoxicity contribute to efficacy once the nanoparticle has reached the tumor's interstitial space. We elaborate on how tumor vascularization and receptor expression vary depending on cancer type, stage of disease, site of implantation, and host species, and review studies which have demonstrated that these variations affect tumor response to nanomedicines. Finally, we show how knowledge of these properties (both of the nanoparticle and the cancer/tumor under study) can be used to design meaningful in vivo tests to evaluate nanoparticle efficacy.
IL-6 Type Cytokine Receptor Complexes: Hexamer, Tetramer or Both? (1999)

The typical protein fold of most cytokines is a bundle of four antiparallel helices. This 'four-helical bundle fold' seems to be unique to cytokines and has not been detected in other proteins. Cytokine receptors, however, can be classified as a subfamily of the immunoglobulin superfamily. Cytokines using the same receptor subunits are grouped into cytokine families. The interleukin-6 (IL-6) type cytokine family comprises six members. IL-6 type cytokines may interact with three receptor subunits instead of the usual two subunits. A tetramer would be the simplest model to describe such a receptor complex, but present orthodoxy describes the active complexes of IL-6 and ciliary neurotrophic factor (CNTF) as hexamers. Here, we summarize the structural and biochemical information on IL-6 type cytokines and discuss interactions between cytokine and individual receptor subunits at alternative positions. Contradictory results regarding the stoichiometry and assembly of signaling receptor complexes are rationalized by a new, unique model. The model stipulates that a ligand-induced transition from an active tetrameric to an inactive hexameric complex serves as a molecular switch that turns off cytokine signals in the presence of supraoptimal cytokine concentrations.
Automated Fluorescent DNA Sequencing (2003)

Fluorescent automated DNA sequencing based on ″one-lane, four-dye″ technology has played a pivotal role in the success of the human genome project. One Applied Biosystems 377 sequencer can produce at least two runs per day of sequence reads averaging 750 bases in length, each run produces up to 96 reads. Improvements in sequencing chemistry (better polymerases and higher sensitivity dyes) have resulted in higher quality, more accurate sequencing data (1,2). This technology will be of enormous value in the next stage of genome sequencing, when the nature of sequence polymorphism in individual genes will be used to understand the complex relationships between genotype and phenotype. Fluorescent DNA sequencing is also rapidly becoming established as the technology of choice in basic research and clinical disciplines; methods for the molecular diagnosis of genetic disorders, pathogen identification, and genetic identification from biological specimens have all been developed and are being utilized in the field of DNA diagnostics (3–5).
Antitumour imidazotetrazines. Part 39. Synthesis of bis(imidazotetrazine)s with saturated spacer groups (2000)

Bis(imidazotetrazine)s (16), related in structure to the antitumour agents mitozolomide (1a) and temozolomide (1b), but linked through the N(3)–N(3′) atoms of the imidazo[5,1-d][1,2,3,5]tetrazine ring-systems, are prepared by interaction of 5-diazoimidazole-4-carboxamide (8) and diisocyanates (15). The presence of the polymethylene linker with/without sulfur and oxygen heteroatoms does not substantially affect the acid stability, base-catalysed decomposition, antitumour activity or DNA base alkylation preference characteristic of the unlinked imidazotetrazines mitozolomide and temozolomide.
A transgenic mouse strain expressing four drug-selectable marker genes (1997)

Murine embryonic stem (ES) cells are commonly cultured on feeder layers of primary murine embryonic fibroblasts (MEFs). Because gene targeting experiments often involve sequential selection for multiple-drug resistance in single ES cell lines, we have developed a new mouse strain which represents an economical donor for the production of multiple-drug resistant MEFs. MEFs prepared from the DR-4 mouse strain displayed resistance to concentrations of the drugs G418, 6-thioguanine, puromycin and hygromycin well above those used normally for the selection of drug-resistant ES cells.
Biochemical and thrombolytic properties of a low molecular weight form (comprising Leu144 through Leu411) of recombinant single-chain urokinase-type plasminogen activator. (1988)

The cDNA encoding a low Mr derivative (residues 144-411) of human single-chain urokinase-type plasminogen activator was cloned, the recombinant low Mr single-chain urokinase-type plasminogen activator (rscu-PA-32k) was expressed in Chinese hamster ovary cells, and the translation product was purified to homogeneity from conditioned cell culture medium. rscu-PA-32k is very similar to intact recombinant single-chain urokinase-type plasminogen activator in terms of its very low activity (120 IU/mg) on a chromogenic substrate for urokinase (pyroglutamylglycylarginine p-nitroanilide), its plasminogen-dependent fibrinolytic activity on fibrin plates (specific activity = 170,000 IU/mg), its plasminogen activating potential, and the lack of specific binding to fibrin. In a rabbit jugular vein thrombosis model, comparable thrombolysis was obtained with rscu-PA-32k as compared to low molecular weight two-chain urokinase (50% lysis at 2.1 and 1.6 mg/kg infused over 4 h). Thrombolysis was associated with much less extensive systemic fibrinogen breakdown with rscu-PA-32k than with two-chain urokinase (residual fibrinogen at 50% lysis of 71 and 10%, respectively). It is concluded that the functional properties of rscu-PA-32k, expressed with a high efficiency, are similar to those of its previously characterized natural counterpart.
The role of impacts (2001)

A quotation from Ursula Marvin headed this chapter in the 1992 edition: “A hypervelocity meteorite impact is an extraordinary event – wreaking change instantaneously. Such a process violates every tenet of uniformitarianism. Largely for this reason, hypotheses of impact origin for craters on the Earth and the Moon were vigorously opposed for the better part of the last [19th] century … research has now established, beyond doubt, the authenticity of impact as a geological process, but … a wide chasm still persists between the views of impact specialists and those of terrestrial geologists” [1]. By 1999 a major philosophical advance had occurred so that it was possible for her to write that “Today we realise that collisions in space are the most fundamental process that has operated throughout the history of the solar system. This is a truly revolutionary insight that requires a fresh vision of the basic tenets of geology” [2].