gebhart/patrepeval huggingface dataset:
Protein structural domains: Analysis of the 3Dee domains database (2001)

The 3Dee database of domain definitions was developed as a comprehensive collection of domain definitions for all three-dimensional structures in the Protein Data Bank (PDB). The database includes definitions for complex, multiple-segment and multiple-chain domains as well as simple sequential domains, organized in a structural hierarchy. Two different snapshots of the 3Dee database were analyzed at September 1996 and November 1999. For the November 1999 release, 7,995 PDB entries contained 13,767 protein chains and gave rise to 18,896 domains. The domain sequences clustered into 1,715 domain sequence families, which were further clustered into a conservative 1,199 domain structure families (families with similar folds). The proportion of different domain structure families per domain sequence family increases from 84% for domains 1-100 residues long to 100% for domains greater than 600 residues. This is in keeping with the idea that longer chains will have more alternative folds available to them. Of the representative domains from the domain sequence families, 49% are in the range of 51-150 residues, whereas 64% of the representative chains over 200 residues have more than 1 domain. Of the representative chains, 8.5% are part of multichain domains. The largest multichain domain in the database has 14 chains and 1,400 residues, whereas the largest single-chain domain has 907 residues. The largest number of domains found in a protein is 13. The analysis shows that over the history of the PDB, new domain folds have been discovered at a slower rate than by random selection of all known folds. Between 1992 and 1997, a constant 1 in 11 new domains deposited in the PDB has shown no sequence similarity to a previously known domain sequence family, and only 1 in 15 new domain structures has had a fold that has not been seen previously. A comparison of the September 1996 release of 3Dee to the Structural Classification of Proteins (SCOP) showed that the domain definitions agreed for 80% of the representative protein chains. However, 3Dee provided explicit domain boundaries for more proteins. 3Dee is accessible on the World Wide Web at http://barton.ebi.ac.uk/servers/3Dee.html.
Antagonists of substance P. Further modifications of SP antagonists obtained by replacing either positions 7, 9 or 7, 8 and 11 of SP with D-amino acid residues (1986)

Antagonists of SP and the C-terminal (6-11)-hexapeptide have been obtained by multiple D-amino acid substitutions in various positions of SP and by protecting the N alpha-Arg1 and N epsilon Lys3 amino groups with benzyloxycarbonyl groups. On the guinea pig ileum a number of these antagonized both SP and the hexapeptide. Except [N alpha-Z-Arg1,D-Pro2,N epsilon-Z-Lys3,Asn5,Arg6,D-Phe7,D-Trp9]-SP-OMe (4) and the corresponding amide 7, which were more potent antagonists of SP than the hexapeptide, all the others, e.g., [N alpha-Z-Arg1,D-Pro2,4,N epsilon-Z-Lys3,D-Phe7,8,Sar9,D-Met11]-SP-OMe (9), [N alpha-Z-Arg1,D-Pro2,4,N epsilon-Z-Lys3,D-Phe7,8,Sar9,MeLeu10,D-Met11]-SP -OMe (11), were more potent antagonists of the hexapeptide. On the rat spinal cord preparation, most of the antagonists were only active against the hexapeptide. A few antagonized SP, but these also reduced carbachol or both carbachol and glutamate responses. Two of the antagonists, [D-Pro2,Asn5,Lys6,D-Phe7,D-Trp9]-SP-OMe (2) and [Boc-D-Pro4,D-Phe7,8,Sar9,D-Met11]-SP(4-11)-OMe (10), were inactive on the ileum but still antagonized the hexapeptide on the spinal cord. The smallest peptides to antagonize SP and the hexapeptide were two heptapeptides, 6 and 21, [Z-Asn5,Arg6,D-Phe7,8,Gly9 psi (CH2S)D-Leu10,D-Met11]-SP(5-11)-OMe (21) being more potent than 6. None of the antagonists showed significant analgesic activity without side effects. Some of the antagonists were shown to release histamine from isolated rat peritoneal cells.
Amphipathic Benzenes Are Designed Inhibitors of the Estrogen Receptor α/Steroid Receptor Coactivator Interaction (2008)

We report here on the design, synthesis, and evaluation of small molecule inhibitors of the interaction between a steroid receptor coactivator and estrogen receptor alpha. These inhibitors are based upon an amphipathic benzene scaffold whose hydrophobic face mimics the leucine-rich alpha-helical consensus sequence on the steroid receptor coactivators that interacts with a shallow groove on estrogen receptor alpha. Several of these molecules are among the most potent inhibitors of this interaction described to date and are active at low micromolar concentrations in both in vitro models of estrogen receptor action and in cell-based assays of estrogen receptor-mediated coactivator interaction and transcription.
[Ongoing improvement in the quality of chronic prescriptions at a primary care center: a 5-year follow-up]. (1994)

A continuous improvement in the quality of prescription for the chronically ill has been observed over the last 5 years and can be attributed to the primary care team.
The Influence of Carboxyl Groups on the Photoluminescence of Mercaptocarboxylic Acid-Stabilized CdTe Nanoparticles (2002)

The CdTe nanoparticles were prepared in aqueous solution using different mercaptocarboxylic acids such as 3-mercaptopropionic acid (MPA) and thioglycolic acid (TGA) as stabilizing agents following the synthetic route described in ref 9. The pH-dependent photoluminescence (PL) of MPA- and TGA-stabilized CdTe nanoparticles was systematically investigated before and after addition of poly(acrylic acid) (PAA) into the CdTe solutions. Experimental results reveal that lowering the pH can increase the PL efficiency of both MPA- and TGA-stabilized CdTe. Moreover, the PL of the CdTe can further be increased in the presence of PAA in low pH range. X-ray photoelectron spectroscopy (XPS) was employed to investigate the interaction between the carboxyl groups from PAA and CdTe nanoparticles which were assembled in polymer matrix by a layer-by-layer self-assembly method to exclude interference from other species in CdTe solutions. XPS results demonstrate that the S/Te ratio of CdTe particles decreases after the addition of PAA, which strongly suggests that PAA can strongly interact with CdTe nanoparticles via the coordination between carboxyl groups and cadmium ions on the particle surface. As a result, the PL efficiency of the mercaptocarboxylic acid-stabilized CdTe nanoparticles is enhanced in acidic range.
Integrated information retrieval for law in a hypertext environment (1988)

A prototype information retrieval system for lawyers, Justus, has been developed on a Sun workstation to run in a Guide hypertext environment. The hypertext database is created automatically by Justus from machine readable versions of the ordinary printed texts, ideally the publisher's typesetting tapes. The database incorporates primary legal sources, such as statutes and cases, and secondary sources, such as textbooks and a dictionary. Initially, the lawyer may select any document in the system. From this initial document, he may access any other document, or part of any other document, to which reference is made. Reference selection is by a pointing device, such as a mouse. There is no limit on the number of selections that can be made, and no restrictions on the path through the system.
Effect of renal failure on gastrointestinal hormones (1979)

Abstract The development of sensitive, specific radioimmunoassays has enabled study of gastrointestinal hormones in various disease states. Since the findings that the kidney catabolizes gastrin and serum gastrin is elevated in chronic renal failure and in anephric patients, other hormones have been studied in these conditions. Cholecystokinin (CCK), GIP, glucagon, and secretin are all elevated in chronic renal failure and the degree of elevation is correlated with the severity of renal impairment. Hemodialysis leads to a lowering of gastrin and GIP but has no effect on CCK or glucagon. Levels of gastrin return to normal following successful renal transplantation. The role that these elevated hormone levels play in altered gastrointestinal function in renal failure is uncertain .
Complex regulation of the DNA-binding activity of p53 by phosphorylation: differential effects of individual phosphorylation sites on the interaction with different binding motifs. (1996)

The tumor suppressor protein p53 exists in different phosphorylation states depending on the cellular environment and perhaps the stage of the cell cycle. These different phosphorylation states can be mimicked in the baculovirus expression system by employing the phosphatase inhibitor okadaic acid. Hyperphosphorylation of p53, particularly of Ser313 and/or Ser309, stimulated its DNA binding activity (Fuchs, Hecker and Scheidtmann, Eur. J. Biochem. 228, 625, 1995). Here we show that hyperphosphorylation of p53 has different effects on its DNA-binding activity, depending on the phosphorylation sites and the binding motif: (i) Phosphorylation of amino-terminal sites appeared to reduce binding to the RGC consensus motif, whereas additional phosphorylation of both, Ser313 and Ser309 led to enhanced binding. (ii) Upon hyperphosphorylation, binding to the RGC motif was enhanced whereas binding to the p53 response element of the bax1 gene promoter was diminished. (iii) DNA binding was also greatly enhanced by antibodies Pab 122 and 421 directed against the carboxyl terminus, but this latter effect was superimposed by the phosphorylation state of p53. Thus, the DNA binding activity of p53 appears to be regulated in a complex way in that (i) binding to a given sequence motif may be regulated by differential phosphorylation and/or by interaction with other factors; (ii) binding to different motifs may be modulated in opposite ways. Thus, the different genes that are regulated by p53 may be differently affected by these parameters.
Nuclear hormone receptors and rational drug discovery (1991)

Conference Article| November 01 1991 Nuclear hormone receptors and rational drug discovery Stephen Green Stephen Green 1Imperial Chemical Industries PLC, Central Toxicology Laboratory, Cell and Molecular Biology Section, Alderley Park, Macclesfield, Cheshire, SKI0 4TJ, U.K. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Received: August 05 1991 Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1991 Biochemical Society1991 Biochem Soc Trans (1991) 19 (4): 894–897. https://doi.org/10.1042/bst0190894 Article history Received: August 05 1991 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Stephen Green; Nuclear hormone receptors and rational drug discovery. Biochem Soc Trans 1 November 1991; 19 (4): 894–897. doi: https://doi.org/10.1042/bst0190894 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: GR, glucocorticoid receptor, ER, oestrogen receptor, RARα, retinoic acid receptor, TR, thyroid hormone receptor, TRβ, murine-thyroid-hormone-receptor β, mPPAR, mouse-peroxisome-proliferator-activated receptor, CAT, chloramphenicol acetyl transferase gene This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL‐1β/IL‐1R1/MyD88/NF‐κB pathway (2016)

Interleukin (IL)-1β plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. The production of IL-1β is dependent upon caspase-1-containing multiprotein complexes called inflammasomes and IL-1R1/MyD88/NF-κB pathway. In this study, we explored whether a potential anti-fibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and anti-fibrotic effects through suppressing activation of NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome and the IL-1β/IL-1R1/MyD88/NF-κB pathway in vivo and in vitro. Male C57BL/6J mice were intratracheally injected with Bleomycin (BLM) or saline. Fluorofenidone was administered throughout the course of the experiment. Lung tissue sections were stained with haemotoxylin and eosin and Masson's trichrome. Cytokines were measured by ELISA, and α-smooth muscle actin (α-SMA), fibronectin, collagen I, caspase-1, IL-1R1, MyD88 were measured by Western blot and/or RT-PCR. The human actue monocytic leukaemia cell line (THP-1) were incubated with monosodium urate (MSU), with or without FD pre-treatment. The expression of caspase-1, IL-1β, NALP3, apoptosis-associated speck-like protein containing (ASC) and pro-caspase-1 were measured by Western blot, the reactive oxygen species (ROS) generation was detected using the Flow Cytometry, and the interaction of NALP3 inflammasome-associated molecules were measured by Co-immunoprecipitation. RLE-6TN (rat lung epithelial-T-antigen negative) cells were incubated with IL-1β, with or without FD pre-treatment. The expression of nuclear protein p65 was measured by Western blot. Results showed that FD markedly reduced the expressions of IL-1β, IL-6, monocyte chemotactic protein-1 (MCP-1), myeloperoxidase (MPO), α-SMA, fibronectin, collagen I, caspase-1, IL-1R1 and MyD88 in mice lung tissues. And FD inhibited MSU-induced the accumulation of ROS, blocked the interaction of NALP3 inflammasome-associated molecules, decreased the level of caspase-1 and IL-1β in THP-1 cells. Besides, FD inhibited IL-1β-induced the expression of nuclear protein p65. This study demonstrated that FD, attenuates BLM-induced pulmonary inflammation and fibrosis in mice via inhibiting the activation of NALP3 inflammasome and the IL-1β/IL-1R1/MyD88/ NF-κB pathway.
Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells (2001)

Dendritic cells (DCs) that acquired antigen from apoptotic tumor cells are able to induce major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes and antitumor immunity. In the present study, we investigated the efficiency of antitumor immunity derived from DCs that had phagocytosed apoptotic/necrotic BL6-10 melanoma cells compared with that of DCs pulsed with the tumor mTRP2 peptide. Our data showed that phagocytosis of apoptotic/necrotic tumor cells resulted in maturation of DCs with up-regulated expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5. These mature DCs displayed enhanced migration toward the CC chemokine MIP-3beta in a chemotaxis assay in vitro and to the regional lymph nodes in an animal model in vivo. Our data also showed that vaccination with DCs that had phagocytosed apoptotic/necrotic BL6-10 cells was able to (i) more strongly stimulate allogeneic T-cell proliferation in vitro, (ii) induce an in vivo Th1-type immune response leading to more efficient tumor-specific cytotoxic CD8(+) T-cell-mediated immunity and (iii) eradicate lung metastases in all 6 vaccinated mice compared with mice vaccinated with DCs pulsed with the tumor mTRP2 peptide, in which lung metastases were reduced (mean number of 16 per mouse) but not completely eradicated. Therefore, DCs that had phagocytosed apoptotic/necrotic tumor cells appear to offer new strategies in DC cancer vaccines.
INTERRELATIONSHIPS OF THE PATHWAYS OF mRNA DECAY AND TRANSLATION IN EUKARYOTIC CELLS (1996)

While the potential importance of mRNA stability to the regulation of gene expression has been recognized, the structures and mechanisms involved in the determination of individual mRNA decay rates have just begun to be elucidated, particularly in mammalian systems and yeast. It is now well established that mRNA decay is not a default process, in which an array of nonspecific nucleases degrades indiscriminately based on target size or ribosome protection of the substrate. Rather, like transcription, RNA processing, and translation, mRNA decay is a precise process dependent on a variety of specific cis-acting sequences and trans-acting factors. Entry into the pathways of mRNA decay is triggered by at least three types of initiating event: poly(A) shortening, arrest of translation at a premature nonsense codon, and endonucleolytic cleavage. Steps subsequent to poly(A) shortening or premature translational termination converge in a pathway that progresses from removal of the 5' cap to exonucleolytic digestion of the body of the mRNA. mRNA fragments generated by endonucleolytic cleavage are most likely removed by exonucleolytic decay as well, but these events have not been characterized in detail. Nucleases and other factors (including mRNA sequence elements and autoregulatory proteins) required for the promotion or inhibition of these pathways have been identified by both biochemical and genetic methods and systematic attempts to understand their respective roles have begun. mRNA sequences whose presence or absence has marked effects on mRNA decay rates include the ubiquitous cap and poly(A) tail, sequences that comprise endonuclease cleavage sites, and sequences that promote poly(A) shortening. The latter are found in the 3'-UTR (untranslated region) and in coding regions. Evidence that poly(A) stimulates translation initiation, that some destabilization sequences must be translated in order to function, and that premature translation termination promotes rapid mRNA decay indicates a close linkage between the elements regulating mRNA decay and components of the protein synthesis apparatus. This linkage, and other data, leads us to propose a model for a functional mRNP. In this model, interactions between factors associated with opposite ends of an mRNA stimulate translation initiation and minimize the rate of entry into the pathways of mRNA decay. Events that initiate mRNA decay are postulated to be those that can disrupt this functional complex and create substrates for exonucleolytic digestion.
Efficient methods for simulating highly nonlinear multi-rate circuits (1997)

Widely-separated time scales appear in many electronic circuits, making traditional analysis difficult or impossible if the circuits are highly nonlinear. In this paper, an analyticalformulation and numerical methods are presented for treating strongly nonlinear multi-rate circuits effectively. Multivariate functions in the time domain are used to capturewidely separated rates efficiently, and a special partial differential equation (the MPDE) is shown to relate the multivariate forms of a circuit's signals. Time-domain and mixedfrequency-time simulation algorithms are presented for solving the MPDE. The new methods can analyze circuits that are both large and strongly nonlinear. Compared to traditional techniques, speedups of more than two orders of magnitude, as well as improved accuracy, are obtained.
Frequency and Pattern of Transposition of the Maize Transposable Element Ds in Transgenic Rice Plants (2000)

Two kinds of T-DNA constructs, I-RS/dAc-I-RS and Hm(R)Ds, carrying a non-autonomous transposable element of Ac of maize were introduced into rice plants by Agrobacterium-mediated gene transfer. Six transgenic rice plants identified as containing a single copy of the element were crossed with two transgenic rice plants carrying a gene for Ac transposase under the control of the cauliflower mosaic virus 35S promoter. In F2 progenies, excision of the element was detected by PCR analysis and re-integration of the element was investigated by Southern blot analysis. The frequency of the excision of the element was found to vary from 0 to 70% depending on the crossing combination. The frequency of the number of individual transposition events out of the total number of F2 plants with germinal excision was 44% in one crossing combination and 38% in the other. In the most efficient case, 10 plants with independent transposition were obtained out of the 49 F2 plants tested. Linkage analysis of the empty donor site and the transposed Ds-insertion site in F3 plants demonstrated that one of five Ds-insertion sites was not linked to the empty donor site. The transgenic rice obtained in this study can be used for functional genomics of rice.
Highly compact imaging using Bessel beams generated by ultraminiaturized multi-micro-axicon systems (2012)

Employing Bessel beams in imaging takes advantage of their self-reconstructing properties to achieve small focal points while maintaining a large depth of focus. Bessel beams are efficiently generated using axicons, and their utility in scanning imaging systems, such as optical coherence tomography (OCT), has been demonstrated. As these systems are miniaturized to allow, for example, endoscopic implementations, micro-axicons are required to assure the maintenance of a large depth of focus. We demonstrate here the design, fabrication, and application of molded micro-axicons for use in silicon-based micro-optical benches. It is shown that arrangements of multiple convex and concave axicons may be implemented to optimize the depth of focus in a miniaturized OCT system, using a telescopic optical arrangement of considerably shorter optical system length than that achievable with classical micro-optics.
Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction (2008)

The caspase recruitment domain (CARD) of intracellular adaptors and sensors plays a critical role in the assembly of signaling complexes involved in innate host defense against pathogens and in the regulation of inflammatory responses. The cytosolic receptor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA in a 5'-triphosphate-dependent manner and initiates an antiviral signaling cascade. Upon viral infection, the N-terminal CARDs of RIG-I undergo the K(63)-linked ubiquitination induced by tripartite motif protein 25 (TRIM25), critical for the interaction of RIG-I with its downstream signaling partner MAVS/VISA/IPS-1/Cardif. Here, we demonstrate the distinct roles of RIG-I first and second CARD in TRIM25-mediated RIG-I ubiquitination: TRIM25 binds the RIG-I first CARD and subsequently ubiquitinates its second CARD. The T(55)I mutation in RIG-I first CARD abolishes TRIM25 interaction, whereas the K(172)R mutation in the second CARD eliminates polyubiquitin attachment. The necessity of the intact tandem CARD for RIG-I function is further evidenced by a RIG-I splice variant (SV) whose expression is robustly up-regulated upon viral infection. The RIG-I SV carries a short deletion (amino acids 36-80) within the first CARD and thereby loses TRIM25 binding, CARD ubiquitination, and downstream signaling ability. Furthermore, because of its robust inhibition of virus-induced RIG-I multimerization and RIG-I-MAVS signaling complex formation, this SV effectively suppresses the RIG-I-mediated IFN-beta production. This study not only elucidates the vital role of the intact tandem CARD for TRIM25-mediated RIG-I activation but also identifies the RIG-I SV as an off-switch regulator of its own signaling pathway.