gebhart/patrepeval huggingface dataset:
Acylation of ester enolates by N-methoxy-N-methylamides: an effective synthesis of .beta.-keto esters (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcylation of ester enolates by N-methoxy-N-methylamides: an effective synthesis of .beta.-keto estersJames A. Turner and Wendy S. JacksCite this: J. Org. Chem. 1989, 54, 17, 4229–4231Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/jo00278a047https://doi.org/10.1021/jo00278a047research-articleACS PublicationsRequest reuse permissionsArticle Views1644Altmetric-Citations58LEARN 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
Effect of excess folates and deoxyinosine on the activity and site of action of 5-fluorouracil. (1981)

Abstract The present study concerns the basis of the effects of high levels of folinic acid (CF) and deoxyinosine (dIno) on the potency and site of action of 5-fluorouracil (FUra) in mouse sarcoma (Sarcoma 180) and human carcinoma cells (Hep-2) in vitro. Sarcoma 180 cells are 50 times more sensitive to FUra than are Hep-2 cells, and thymidylate synthetase (dTMP synthetase) inhibition is growth limiting in Sarcoma 180 but not in Hep-2. Cells were exposed for 3 hr to varied concentrations of FUra alone or in combination with 10 µm CF and/or 1 mm dIno, and the following parameters were determined: (a) the subsequent growth (5 or 6 days) in FUra-free Medium 1640 with or without either 30 µm thymidine or 1 mm 2′-deoxyuridine (dUrd); (b) metabolism of FUra; (c) activity of dTMP synthetase in cell extracts; and (d) incorporation of [2-14C]dUrd at 0, 3, 6, 24, and 48 hr following FUra exposure. In both cell lines, dIno increased the cellular content of unbound 5-fluoro-2′-deoxyuridine-5′-monophosphate up to 100 µm and the inhibition of dTMP synthetase. The potency of FUra, as measured by growth inhibition, was increased only against Sarcoma 180 and not against Hep-2. A very rapid recovery of enzyme activity occurred after dIno, and dTMP synthetase inhibition did not become growth limiting for Hep-2. In both cell lines, 10 µm CF (1000 times more than required for growth) potentiated 3-fold the growth inhibition by FUra. This excess CF did not affect the extent of dTMP synthetase inhibition when measured immediately after FUra. Instead, the potentiating effect of CF is due to the stabilization of the enzyme-5-fluoro-2′-deoxyuridine-5′-monophosphate complex as evidenced by (a) a marked decrease in the ability of 1 mm dUrd to rescue Sarcoma 180 cells after treatment with FUra or Hep-2 cells after treatment with 5-fluoro-2′-deoxyuridine, without effect on the rescue with 2′-deoxythymidine and (b) a marked slow-down in the spontaneous recovery of dTMP synthetase activity after FUra or after FUra and dIno. In all conditions, the recovery of dTMP synthetase activity reached a limit at 6 hr after FUra removal. An impressive correlation was observed in Sarcoma 180 cells between the dTMP synthetase activities (measured by dUrd incorporation), which were reached 6 hr after FUra removal, and growth, which was measured at 5 days. Effects identical to those of 10 µm CF were obtained with 300 µm folic acid or 10 µmN5-methyltetrahydrofolic acid. A maximum potentiation of growth inhibition (10-fold) occurred after combinations of FUra with excess folates and dIno. It appears that the rate of recovery of dTMP synthetase activity plays a more significant role in the potency and site of action of FUra than does the amount of 5-fluoro-2′-deoxyuridine-5′-monophosphate which is formed and that this recovery can be greatly retarded with an excess of vitamins such as folate or CF.
Effective Disruption of Phosphoprotein−Protein Surface Interaction Using Zn(II) Dipicolylamine-Based Artificial Receptors via Two-Point Interaction (2006)

Protein phosphorylation is ubiquitously involved in living cells, and it is one of the key events controlling protein−protein surface interactions, which are essential in signal transduction cascades. We now report that the small molecular receptors bearing binuclear Zn(II)-Dpa can strongly bind to a bis-phosphorylated peptide in a cross-linking manner under neutral aqueous conditions when the distance between the two Zn(II) centers can appropriately fit in that of the two phosphate groups of the phosphorylated peptide. The binding property was quantitatively determined by ITC (isothermal titration calorimetry), induced CD (circular dichroism), and NMR. On the basis of these findings, we demonstrated that these types of small molecules were able to effectively disrupt the phosphoprotein−protein interaction in a phosphorylated CTD peptide and the Pin1 WW domain, a phosphoprotein binding domain, at a micromolar level. The strategy based on a small molecular disruptor that directly interacts with phosphoprotein is unique and should be promising in developing a designer inhibitor for phosphoprotein−protein interaction.
Feedback Techniques for Intra-Media Continuity and Inter-Media Synchronization in Distributed Multimedia Systems (1993)

Future advances in networking and storage will make it feasible to build multimedia on-demand servers that provide services similar to those of a neighbourhood videotape rental store over metropolitan area networks such as B-ISDN. Such multimedia servers can support real-time retrieval of multimedia objects by users onto their ISDN videophones and audiophones for playback. The design of techniques and protocols for providing continuous and synchronous access to multimedia services constitutes the subject matter of this paper. In future integrated networks, mediaphones that possess bare minimum capability to playback media but which lack the sophistication to run elaborate time synchronization protocols, may be connected directly to the network. We present rate-based feedback strategies by which, during retrieval, a multimedia server uses light-weight messages called feedback units transmitted periodically to mediaphones, to accurately estimate the playback instants of media units. Using these estimates, the multimedia server detects impending playback discontinuities due to buffer overruns or starvations at mediaphones, and preventively readjusts media transmission so as to avoid either of these anomalies. Given the available buffer sizes at mediaphones, we present methods by which a multimedia server can determine the minimum rate at which feedback units must be transmitted to it by the mediaphones, so as to maintain continuity of media playback. In order to guarantee synchronous playback at mediaphones, we first propose a bounded buffering technique which uses buffering limitations, at the slave mediaphones to automatically enforce bounds on the asynchrony among mediaphones. Although simple and easy to implement, this technique may entail a large average asynchrony, in order to avoid which we propose a multiple feedback synchronization technique. We present initial performance comparisons of the effectiveness of these synchronization techniques. The techniques for intra-media continuity and inter-media synchronization presented in this paper from the basis of a prototype multimedia on-demand server being developed at the UCSD Multimedia Laboratory.
Hierarchical assembly of inorganic nanostructure building blocks to octahedral superstructures—a true template-free self-assembly (2007)

A room temperature, template-free, wet chemical synthesis of ceria nanoparticles and their long term ageing characteristics are reported. High resolution transmission electron microscopy and UV-visible spectroscopy techniques are used to observe the variation in size, structure and oxidation state, respectively as a function of time. The morphology variation and the hierarchical assembly (octahedral superstructure) of nanostructures are imputed to the inherent structural aspects of cerium oxide. It is hypothesized that the 3-5 nm individual building blocks will undergo an intra-agglomerate re-orientation to attain the low energy configuration. This communication also emphasizes the need for long term ageing studies of nanomaterials in various solvents for multiple functionalities.
Self-Assembled Monolayers That Resist the Adsorption of Proteins and the Adhesion of Bacterial and Mammalian Cells (2001)

This paper examines the hypothesis that surfaces resistant to protein adsorption should also be resistant to the adhesion of bacteria (Staphylococcus aureus, Staphylococcus epidermidis) and the attachment and spreading of mammalian cells (bovine capillary endothelial (BCE) cells). The surfaces tested were those of self-assembled monolayers (SAMs) terminated with derivatives of tri(sarcosine) (Sarc), N-acetylpiperazine, permethylated sorbitol, hexamethylphosphoramide, phosphoryl choline, and an intramolecular zwitterion (−CH2N+(CH3)2CH2CH2CH2SO3-) (ZW); all are known to resist the adsorption of proteins. There seems to be little or no correlation between the adsorption of protein (fibrinogen and lysozyme) and the adhesion of cells. Surfaces terminated with derivatives of Sarc and N-acetylpiperazine resisted the adhesion of S. aureus and S. epidermidis as well as did surfaces terminated with tri(ethylene glycol). A surface that presented Sarc groups was the only one that resisted the adhesion of BCE cells as well as did a surface terminated with tri(ethylene glycol). The attachment of BCE cells to surfaces could be patterned using SAMs terminated with derivatives of Sarc, N-acetylpiperazine, phosphoramide, and the ZW as the attachment-resistant component and methyl-terminated SAMs as the adhesive component.
New Approach for the Detection of Peptide- and Protein-Based Radicals Using a Pre-Fluorescent Probe (2006)

A novel application for pre-fluorescent probes in the detection of peptide- and protein-based radicals is proposed. Pre-fluorescent probes combine a fluorescent moiety labeled with a paramagnetic nitroxide that acts as a fluorescence quencher. Trapping of a radical by the nitroxide group restores the fluorescence properties. The increase in fluorescence intensity with time reflects the formation and quenching of free radicals and can be employed for the quantitative evaluation of yields and kinetics. In this test system, the pre-fluorescent probe 4-(9-acridinecarbonate)-2,2,6,6-tetramethylpiperidinyl-1-oxyl radical (Ac-Tempo), in which an acridine moiety was labeled with 2,2,6,6-tetramethylpiperidinyl-1-oxy (Tempo), was employed to probe peptide- and protein-based radicals. Peptide-based radicals were generated through the reaction between horseradish peroxidase (HRP)/H(2)O(2) and a derivative of tyrosine. Protein-based radicals were generated through the reaction between myoglobin (Mb) and H(2)O(2). In both cases the Ac-Tempo was found, using a combination of high-performance liquid chromatography (HPLC) and mass spectrometry, to be converted into fluorescent acridine (Ac)-piperidine (4-(9-acridinecarbonate)-2,2,6,6-tetramethylpiperidine).
Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. (1985)

Antibodies against the T3-antigen receptor complex can activate the human T cell line, Jurkat, to produce interleukin 2 (2-5). This activation is initiated by a receptor-mediated increase in the concentration of free cytoplasmic calcium ions [Ca2+]i (3, 4). In this communication, we investigate the mechanism by which the receptor complex increases [Ca2+ )i in Jurkat cells. The initial receptor-mediated change in [Ca2+]i can occur when extracellular Ca2+ is depleted by EGTA. Perturbation of the T cell antigen receptor, therefore, generates a signal which mobilizes Ca2+ from intracellular stores. As inositol trisphosphate appears to function as such a signal for certain hormone receptors, we measured the levels of inositol trisphosphate and of the other inositol phosphate compounds in Jurkat. Antibodies to either the antigen receptor heterodimer or T3 determinants result in marked elevations of all three inositol phosphates. These changes in inositol phosphates are not secondary to the receptor-mediated increases in [Ca2+]i as demonstrated by the inability of the Ca2+ ionophore, ionomycin, to affect the levels of any of these compounds. In concentrations between 0.1 and 1 microM, purified inositol trisphosphate releases Ca2+ from permeabilized Jurkat cells. Taken together, these data indicate that, during activation, perturbation of the T3-antigen receptor complex generates inositol trisphosphate. This compound functions as an intracellular signal to release Ca2+ from intracellular stores, leading to increases in [Ca2+]i.
Two Cyclin-Dependent Kinases Promote RNA Polymerase II Transcription and Formation of the Scaffold Complex (2004)

Three cyclin-dependent kinases, CDK7, -8, and -9, are specifically involved in transcription by RNA polymerase II (Pol II) and target the Pol II C-terminal domain (CTD). The role of CDK7 and CDK8 kinase activity in transcription has been unclear, with CDK7 shown to have variable effects on transcription and CDK8 suggested to repress transcription and/or to target other gene-specific factors. Using a chemical genetics approach, the Saccharomyces cerevisiae homologs of these kinases, Kin28 and Srb10, were engineered to respond to a specific inhibitor and the inhibitor was used to test the role of these kinases in transcription in vivo and in vitro. In vitro, these kinases can both promote transcription, with up to 70% of transcription abolished when both kinases are inhibited together. Similarly, in vivo inhibition of both kinases together gives the strongest decrease in transcription, as measured by chromatin immunoprecipitation of Pol II. Kin28 and Srb10 also have overlapping roles in promoting ATP-dependent dissociation of the preinitiation complex (PIC) into the Scaffold complex. Using the engineered kinases and an ATP analog, specific kinase substrates within the PIC were identified. In addition to the previously known substrate, the Pol II CTD, it was found that Kin28 phosphorylates two subunits of Mediator and Srb10 targets two subunits of TFIID for phosphorylation.
Cellular and Humoral Immunity against Vaccinia Virus Infection of Mice (2004)

Despite the widespread use of vaccinia virus (VV) as a vector for other Ags and as the smallpox vaccine, there is little information available about the protective components of the immune response following VV infection. In this study, protection against wild-type VV was evaluated in mice with respect to the relative contributions of CD8(+) T cells vs that of CD4(+) T cells and Ab. C57BL/6 mice primed with the Western Reserve strain of VV mount significant IgM and IgG Ab responses, specific cytotoxic T cell responses, IFN-gamma responses in CD4(+) and CD8(+) T cells, and effectively clear the virus. This protection was abrogated by in vivo depletion of CD4(+) T cells or B cells in IgH(-/-) mice, but was not sensitive to CD8(+) T cell depletion alone. However, a role for CD8(+) T cells in primary protection was demonstrated in MHC class II(-/-) mice, where depleting CD8(+) T cells lead to increase severity of disease. Unlike control MHC class II(-/-) mice, the group depleted of CD8(+) T cells developed skin lesions on the tail and feet and had adrenal necrosis. Adoptive transfer experiments also show CD8(+) T cells can mediate protective memory. These results collectively show that both CD4(+) and CD8(+) T cell-mediated immunity can contribute to protection against VV infection. However, CD4(+) T cell-dependent anti-virus Ab production plays a more important role in clearing virus following acute infection, while in the absence of Ab, CD8(+) T cells can contribute to protection against disease.
Heat-Activated Gene Therapy (1999)

The research goal is to develop heat shock as a modality for optimizing and controlling gene therapy for treating prostate cancer. Heat activatible tissue permeabilizers will increase dissemination of adenoviral vectors throughout solid tumors. The optimal permeabilizer has been identified and its usable ranges of concentration and activating heat shocks have been narrowed sufficiently to begin testing in human Xenograft tumors. A quantitative relationship between time at temperature and induced expression from a truncated heat shock promoter have been established in exponentially growing and plateau phase prostate cancer cells, which is essential for planning and analyzing parallel experiments in solid tumors. This is a fundamental step for establishing controllable expression of transgenes under control of a heat shock promoter within solid tumors. Mammalian expression constructs for expressing diphtheria toxin A and shiga toxin A have been made and tested, and are currently being used to produce adenoviral expression vectors. Fluorescent chimeras of both proteins have also been made, which may prove useful for monitoring gene expression in tumors and normal tissues. The work presented herein represents considerable progress towards achieving the approved tasks, and establishes a solid foundation for developing a form of controllable gene therapy for treating prostate cancer.
Thin film CdTe solar cells-a review (2002)

High-efficiency thin-film CdTe solar cells can be fabricated using various methods ranging from the wet chemical techniques such as electrodeposition to the more conventional semiconductor processing methods such as vacuum evaporation. An examination of these different methods reveals that there are similarities between the postdeposition treatments that the CdTe films are subjected to, before they are used for device fabrication. Some of the cell fabrication techniques are reviewed, and the processing steps common to all methods are highlighted.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ADOPTION OF EUROPEAN UNION'S LAW IN HUNGARY, IN THE AREA OF PRODUCT ADEQUACY (2001)

The EU measures to introduce the internal market came into force on December
31st, 1992. The Council of the European Community produced a Directive, which
describes harmonization of rules issued by the Member Countries concerning
machines. The European Union is an important economic partner of Hungary. We
analyzed the situation concerning machines before the Hungarian connection to
European Community.
Therapeutic potential of serotonin antagonists in depressive disorders (2002)

Although the precise neurochemical imbalances in depression are still unknown, a role for the neurotransmitter 5-hydroxytryptamine (serotonin) has been implicated since the identification of the first effective antidepressants, imipramine and iproniazid. This led to the development of the selective serotonin re-uptake inhibitors which are widely used in the treatment of depression and depressive disorders, including generalised anxiety disorder, social phobia, obsessive compulsive disorder etc. Studies involving chronic administration in rats led to the hypothesis that the different classes of antidepressant treatment produce a common neuroadaptive change, namely an enhancement of serotonin neurotransmission, albeit via different pre and postsynaptic mechanisms. From this, it was suggested that serotonin antagonists should induce similar neuroadaptive changes, either directly or through a potentiation of other antidepressant agents. Here, the profiles of novel serotonin antagonists currently in preclinical development are reviewed and their therapeutic potential is assessed.
Isolation, Chemical Characterization, and Quantitation of Aβ 3-Pyroglutamyl Peptide from Neuritic Plaques and Vascular Amyloid Deposits (1997)

From the neuritic plaques and vascular walls of the brains of patients with Alzheimer disease, we have purified and quantified an A beta peptide which starts at residue 3Glu in the form of pyroglutamyl (A beta3pE). The N-terminally truncated A beta3pE comprised 51% of the A beta in the neuritic plaques. This was followed by 30% starting at position 1Asp which included 20% in the isomerized form (IsoAsp). In contrast, the vascular amyloid only contained an average of 11% in the form of A beta3pE with the major component starting at residue 1Asp (69%), which included only 6% in the form of IsoAsp. The presence of A beta3pE has important structural consequences since it is more hydrophobic than other forms of A beta, thus increasing the insolubility of A beta. In addition, A beta3pE, with its blocked N-terminus to the action of common aminopeptidases, may result in the profuse accumulation of A beta in the neuritic plaques of Alzheimer disease.
Selective over‐expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer (2007)

Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1-4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over-expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1-3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over-expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over-expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling.