gebhart/patrepeval huggingface dataset:
Evaluation and synthesis of amino-hydroxy isoxazoles and pyrazoles as potential glycine agonists (1989)

Except for structurally similar small amino acids, such as alanine, beta-alanine, and serine, compounds acting as glycine-receptor agonists are an unknown class of pharmacological agents. To investigate the potential of small, substituted heterocycles to act as glycine agonists, we have evaluated the similarities between glycine and a series of hydroxy- and amino-substituted pyrazoles and isoxazoles through complementary molecular modeling techniques. Using a "scorecard approach" to determine the overall similarity of projected agonist structures to glycine, we prioritized synthesis and subsequently prepared several novel derivatives. The biological activity of these compounds was compared to that of glycine by using a [3H]strychnine-mediated glycine receptor binding assay. Despite the close similarity in the calculated parameters when compared to glycine, no significant receptor-binding activity was observed for the targeted analogues. These results illustrate the structurally exacting nature of the glycine receptor.
CD4+ T Cells Reactive to Enteric Bacterial Antigens in Spontaneously Colitic C3H/HeJBir Mice: Increased T Helper Cell Type 1 Response and Ability to Transfer Disease (1998)

C3H/HeJBir mice are a new substrain that spontaneously develop colitis early in life. This study was done to determine the T cell reactivity of C3H/HeJBir mice to candidate antigens that might be involved in their disease. C3H/HeJBir CD4+ T cells were strongly reactive to antigens of the enteric bacterial flora, but not to epithelial or food antigens. The stimulatory material in the enteric bacteria was trypsin sensitive and restricted by class II major histocompatibility complex molecules, but did not have the properties of a superantigen. The precursor frequency of interleuken (IL)-2-producing, bacterial-reactive CD4+ T cells in colitic mice was 1 out of 2,000 compared to 1 out of 20,000-25,000 in noncolitic control mice. These T cells produced predominately IL-2 and interferon gamma, consistent with a T helper type 1 cell response and were present at 3-4 wk, the age of onset of the colitis. Adoptive transfer of bacterial-antigen-activated CD4+ T cells from colitic C3H/HeJBir but not from control C3H/HeJ mice into C3H/HeSnJ scid/scid recipients induced colitis. These data represent a direct demonstration that T cells reactive with conventional antigens of the enteric bacterial flora can mediate chronic inflammatory bowel disease.
Delivery and expression of a heterologous antigen on the surface of streptococci (1992)

We have developed a system in which a foreign antigen replaces nearly all of the surface-exposed region of the fibrillar M protein from Streptococcus pyogenes and is fused to the C-terminal attachment motif of the M molecule. The fusion protein is thus expressed on the surface of Streptococcus gordonii, a commensal organism of the oral cavity. The antigen chosen to be expressed within the context of the M6 molecule was the E7 protein (98 amino acids) of human papillomavirus type 16. Stable recombinant streptococci were obtained by integrating genetic constructs into the chromosome, exploiting in vivo homologous recombination. The M6-E7 fusion protein expressed on the S. gordonii surface was shown to be immunogenic in mice. This is the first step in the construction of recombinant live vaccines in which nonpathogenic streptococci as well as other gram-positive bacteria may be used as vectors to deliver heterologous antigens to the immune system.
Synthesis and characterization of a pancreatic trypsin inhibitor homolog and a model inhibitor (1977)

The synthesis and characterization of protein proteinase inhibitor homologues with variations in the amino acid composition in the vicinity of the reactive site should aid the understanding of the mechanism by which inhibition of enzymatic activity occurs. A homologue inhibitor in which the reactive-site residue Ala-16 of basic pancreatic trypsin inhibitor (Kunitz) (BPTI) is replaced by Phe has been synthesized to study the effect of this replacement on the dissociation constants of the enzyme-inhibitor complexes. The replacement of Ala-16 by Phe causes a dramatic increase in the K1 value of the trypsin-BPTI complex while that of the chymotrypsin-BPTI complex remains essentially the same. This cannot be explained simply in terms of increased steric crowding. The Phe replacement probably causes a small change in the local conformation of the reactive site of the inhibitor which leads to a large decrease in the stability of the very tight trypsin-BPTI complex. This conformation change apparently can be tolerated in the less tightly bound chymotrypsin-BPTI complex. On the basis of the known structure of BPTI, a cyclic heptadecapeptide containing one disulfide bond was synthesized as a model inhibitor in order to determine if a smaller peptide can be designed to act as a highly efficient inhibitor for trypsin. This heptadecapeptide which contains all of the amino acid residues of BPTI taking part in the interaction of the proteinase inhibitor with trypsin binds 3 X 10(7) time more weakly to the enzyme than native BPTI does. It thus appears that even though only a small part of the inhibitor molecule enters directly into interaction with the enzyme, the remaining portions of the molecule which hold the structure of the inhibitor rigid are essential for the strong interaction.
Redesigning Enzyme Topology by Directed Evolution (1998)

Genetic selection was exploited in combination with structure-based design to transform an intimately entwined, dimeric chorismate mutase into a monomeric, four-helix-bundle protein with near native activity. Successful reengineering depended on choosing a thermostable starting protein, introducing point mutations that preferentially destabilize the wild-type dimer, and using directed evolution to optimize an inserted interhelical turn. Contrary to expectations based on studies of other four-helix-bundle proteins, only a small fraction of possible turn sequences (fewer than 0.05 percent) yielded well-behaved, monomeric, and highly active enzymes. Selection for catalytic function thus provides an efficient yet stringent method for rapidly assessing correctly folded polypeptides and may prove generally useful for protein design.
Packet loss correlation in the MBone multicast network (2002)

The success of multicast applications such as Internet teleconferencing illustrates the tremendous potential of applications built upon wide-area multicast communication services. A critical issue for such multicast applications and the higher layer protocols required to support them is the manner in which packet losses occur within the multicast network. We present and analyze packet loss data collected on multicast-capable hosts at 17 geographically distinct locations in Europe and the US and connected via the MBone. We experimentally and quantitatively examine the spatial and temporal correlation in packet loss among participants in a multicast session. Our results show that there is some spatial correlation in loss among the multicast sites. However, the shared loss in the backbone of the MBone is, for the most part, low. We find a fairly significant amount of of burst loss (consecutive losses) at most sites. In every dataset, at least one receiver experienced a long loss burst greater than 8 seconds (100 consecutive packets). A predominance of solitary loss was observed in all cases, but periodic losses of length approximately 0.6 seconds and at 30 second intervals were seen by some receivers.
ON THE PHOTOIONIZATION ENERGY THRESHOLD OF TRYPTOPHAN IN AQUEOUS SOLUTIONS (1979)

Abstract— To investigate the existence and energy position of a photoionization threshold. tryptophan (Trp) has been photoionized in desecrated neutral aqueous or alcoholic solution under monochromatic light of variable frequency, in presence of N 2 O to scavenge the photoelectron. Present findings and some literature data converge to show the existence of a threshold for the one photon ionization process. This threshold is located at 4.5 ± 0.1 eV and 4.85 ± 0.1 cV for Trp in aqueous and ethanol solutions. respectively, which corresponds to a lowering with respect to the gas phase ionization potential of 3.4 and 3.0 eV. The photoionization quantum yields for Trp is found about 4 times greater at 250 nm than at Λ cx = 265 nm, where ϕe ‐ 4M =0.080±0.025. In such spectral range. at most one photoelectron out of 4–5 escaping geminate recombination would lead to Trp photodegradation in acrated solutions. These results also point out that the neutral radical Trp. which has been previously observed for Λ cx &gt; 275 nm, i.e. below the ionization threshold energy—would not necessarily derive from Trp + deprotonation or cation‐electron dissociative recombination. Similarly, the opening of the indole ring with formylkynurenine (FK) formation which is observed under aerobic conditions and Λ cx &gt;, 280 nm would not imply an electron attachment on O 2 but reactions such as Trp + 3 O 2 or Trp*+ 3 O 2 or else
Chemically modified carbon electrodes (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemically modified carbon electrodesC. Michael. Elliott and Royce W. MurrayCite this: Anal. Chem. 1976, 48, 8, 1247–1254Publication Date (Print):July 1, 1976Publication History Published online1 May 2002Published inissue 1 July 1976https://pubs.acs.org/doi/10.1021/ac50002a046https://doi.org/10.1021/ac50002a046research-articleACS PublicationsRequest reuse permissionsArticle Views771Altmetric-Citations114LEARN 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
Suture anchor for visceral drainage (1986)

Recently, interest has increased in devising percutaneous techniques for inserting tubes into the stomach [1] and drains into the gallbladder [2] and other hollow viscera [3]. Because there is an inherent risk of spillage of gastric juices, bile, or infected fluids into the abdominal cavity because of invagination [4] of the visceral wall during tract dilatation or malinsertion of drains due to intraperitoneal coiling of guide wires [5], safer methods have been devised, including percutaneous endoscopic gastrostomy [1 ], the Hawkins accordion system [6], and air or balloon distension of the stomach [7]. None of these techniques, however, prevents harmful leakage during early drain exchanges or intravisceral catheter manipulations. A new simple removable retention device is described which serves to firmly anchor the visceral wall against the parietal wall for safer drain insertion.
Immobilization and characterization of γ‐aminobutyric acid on gold surface (2006)

gamma-Aminobutyric acid (GABA) is one of two main inhibitory neurotransmitters in the central nervous system that plays an important role in neuronal function and dysfunction. Immobilization of GABA molecules on a rigid surface in an ordered fashion will provide an opportunity to understand some of the fundamental properties related to its structure and function. In this study, we report a novel strategy for immobilization of bioactive GABA on gold substrate. GABA was immobilized in three consecutive steps, namely gold substrate amination, dextran covalent attachment, and GABA immobilization. Surface chemistry was verified at each step using XPS and FTIR. Bioactivity of GABA immobilized on the gold surface was studied using atomic force microscopy to reveal antigen-antibody binding. Nonspecific protein adsorption on the bioactive surface was analyzed quantitatively using anti-GABA antibody and an enzyme linked nonspecific anti-immunoglobulin-G antibody in an ELISA assay. GABA functionalized surface has high affinity for anti-GABA, while showing significantly low affinity for nonspecific anti-IgG antibody. All these data support the presence of a bio-functional immobilized GABA on the gold surface. In conclusion, we report a novel technique for immobilizing bioactive GABA molecules in an orderly fashion on gold substrates.
Restriction enzyme selection dictates detection range sensitivity in chromatin conformation capture-based variant-to-gene mapping approaches (2020)

Abstract Promoter-focused chromatin conformation techniques directly detect interactions between gene promoters and distal genomic sequences, providing structural information relevant to gene regulation without the excessive non-genic architectural data generated by full scale Hi-C. 3D promoter ‘interactome’ maps are crucial for understanding how epigenomic features like histone modifications and open chromatin, or genetic variants identified in genome wide association studies (GWAS), contribute to biological function. However, variation in sensitivity between such promoter-focused methods, principally due to restriction enzyme selection, has not been systematically assessed. Here, we performed a head-to-head comparison between promoter capture C (PCC) and promoter capture Hi-C (PCHiC) with the respective 4 cutters DpnII and MboI versus 6 cutter HindIII datasets from the same five cell types. While PCHiC generally produces a higher signal to noise ratio for significant interactions in comparison to PCC, we show that DpnII/MboI detects more proximal interactions and shows little overlap with the HindIII detection range. Promoter-interacting genomic regions mapped by 4-cutters are more enriched for regulatory features and disease-associated genetic variation than 6-cutters maps, suggesting that high-resolution maps better capture gene regulatory architectures than do lower resolution approaches.
Glycopeptide Synthesis through endo‐Glycosidase‐Catalyzed Oligosaccharide Transfer of Sugar Oxazolines: Probing Substrate Structural Requirement (2006)

An array of sugar oxazolines was synthesized and tested as donor substrates for the Arthrobacter endo-beta-N-acetylglucosaminidase (Endo-A)-catalyzed glycopeptide synthesis. The experiments revealed that the minimum structure of the donor substrate required for Endo-A catalyzed transglycosylation is a Man beta1-->4-GlcNAc oxazoline moiety. Replacement of the beta-D-Man moiety with beta-D-Glc, beta-D-Gal, and beta-D-GlcNAc monosaccharides resulted in the loss of substrate activity for the disaccharide oxazoline. Despite this, the enzyme could tolerate modifications such as attachment of additional sugar residues or a functional group at the 3- and/or 6-positions of the beta-D-Man moiety, thus allowing a successful transfer of selectively modified oligosaccharides to the peptide acceptor. On the other hand, the enzyme has a great flexibility for the acceptor portion and could take both small and large GlcNAc-peptides as the acceptor. The studies implicate a great potential of the endoglycosidase-catalyzed transglycosylation for constructing both natural and selectively modified glycopeptides.
Curcumin induces cell‐arrest and apoptosis in association with the inhibition of constitutively active NF‐κB and STAT3 pathways in Hodgkin's lymphoma cells (2008)

Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-kappaB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-kappaB and STAT3 in H-RS cells, characterizing the functional consequences. Curcumin is incorporated into H-RS cells and acts inhibiting both NF-kappaB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis, e.g. Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1, survivin, c-myc and cyclin D1. Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL.
Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability (1995)

The sympathetic predominance that characterizes wakefulness decreases during non-REM sleep, is minimal in slow-wave sleep, and surges toward mean awake levels during REM sleep. The autonomic balance is shifted toward parasympathetic predominance during slow-wave sleep. This noninvasive method used to outline autonomic activity achieves results that are in complete agreement with those obtained with direct invasive tools.
Fluoride‐Labile Protecting Groups for the Synthesis of Base‐Sensitive Methyl‐SATE Oligonucleotide Prodrugs (2003)

Abstract Base‐sensitive methyl‐SATE oligonucleotide prodrugs (prooligos) were synthesized using fluoride‐labile protection groups on the nucleobases and on certain internucleosidic phosphate linkages. The combination of [( tert ‐butyl)(diphenyl)silyloxymethyl]benzoyl (SiOMB) and (trimethylsilyl)ethyl (TSE) groups is well adapted for synthesis of these compounds using phosphoramidite chemistry on a solid support. The prooligo was anchored on the support via a phosphoramidate linkage. A final treatment with Et 3 N·3HF in THF efficiently releases the prooligo from the solid support and cleaves the SiOMB and TSE groups. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
Characterization and molecular cloning of the mRNA for the heavy (epsilon) chain of rat immunoglobulin E. (1982)

We report a study of the mRNA for the heavy (epsilon) chain of rat IgE. Cytoplasmic RNA was prepared from the two rat immunocytomas IR2 and IR162 and fractionated by sucrose gradient centrifugation. An enriched fraction containing approximately 5% mRNA for the epsilon chain was obtained in this way. When translated in vitro, it produced a 59,000-dalton polypeptide, which in the presence of a membrane fraction yielded a 90,000-dalton polypeptide, presumably through posttranslational modification. Both polypeptides were precipitated by rabbit antisera that were monospecific for rat epsilon chains. The epsilon chain mRNA was estimated to be approximately 2200 nucleotides long and constitutes a minute fraction in the total mRNA both in the IR2 and the IR162 tumors, unlike the mRNA for light chains. Double-stranded cDNA copies prepared frm the RNA fraction, which was enriched for epsilon chain mRNA, were inserted into the Pst I cleavage site of the pBR322 vector. Twenty clones with inserts exceeding 1000 base pairs were used for selection of mRNA from the IR2 tumor. By in vitro translation of the selected mRNA, one clone was identified that yielded a polypeptide with the same size as the unprocessed epsilon chain. The nucleotide sequence was determined for part of the inserted cDNA in this candidate clone and was found to be homologous to a sequence in the constant region (C) of the human epsilon chain. In this communication we report a sequence from the C epsilon 3 domain of the rat IgE. When compared to the corresponding sequence of human IgE, 55% of the amino acids in the rat sequence were found to be conserved.
Atomic Structure of Adenosine Deaminase Complexed with a Transition-State Analog: Understanding Catalysis and Immunodeficiency Mutations (1991)

The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. The structure is folded as an eight-stranded parallel alpha/beta barrel with a deep pocket at the beta-barrel COOH-terminal end wherein the inhibitor and a zinc are bound and completely sequestered. The presence of the zinc cofactor and the precise structure of the bound analog were not previously known. The 6R isomer of the analog is very tightly held in place by the coordination of the 6-hydroxyl to the zinc and the formation of nine hydrogen bonds. On the basis of the structure of the complex a stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles. A molecular explanation of a hereditary disease caused by several point mutations of an enzyme is also presented.
Probing the oxygen binding site of cytochrome c oxidase by cyanide. (1994)

Cyanide binding to cytochrome c oxidase has been investigated by sequential mixing and rapid scan stopped flow spectroscopy. Double mixing experiments confirm earlier reports that cyanide binds rapidly to partially reduced enzyme species formed in turnover. The absorbance/time/wavelength matrices, captured during the onset of cyanide inhibition of cytochrome c oxidase by rapid scan stopped flow, were analyzed by singular value decomposition and the spectral contributions of the chromophores separated. Examination of the time courses and amplitudes of the spectral signals provide evidence that entry of a single (1-1.3) electron into the enzyme is sufficient to trigger rapid cyanide binding. This electron resides predominantly on the cytochrome a/CuA pair in the inhibited enzyme. In addition, although cytochrome a3 remains oxidized, it does not appear to be the site for the initial inhibitory binding of cyanide. Our data suggest that CuB2+ is the initial binding site.
A desk supporting computer-based interaction with paper documents (1992)

Before the advent of the personal workstation, office work practice revolved around the paper document. Today the electronic medium offers a number of advantages over paper, but it has not eradicated paper from the office. A growing problem for those who work primarily with paper is lack of direct access to the wide variety of interactive functions available on personal workstations. This paper describes a desk with a computer-controlled projector and camera above it. The result is a system that enables people to interact with ordinary paper documents in ways normally possible only with electronic documents on workstation screens. After discussing the motivation for this work, this paper describes the system and two sample applications that can benefit from this style of interaction: a desk calculator and a French to English translation system. We describe the design and implementation of the system, report on some user tests, and conclude with some general reflections on interacting with computers in this way.