gebhart/patrepeval huggingface dataset:
Branch specificity of bovine colostrum CMP-sialic acid: Gal beta 1—4GlcNAc-R alpha 2—6-sialyltransferase. Sialylation of bi-, tri-, and tetraantennary oligosaccharides and glycopeptides of the N-acetyllactosamine type. (1987)

Using 500-MHz 1H NMR spectroscopy we have investigated the branch specificity that bovine colostrum CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase shows in its sialylation of bi-, tri-, and tetraantennary glycopeptides and oligosaccharides of the N-acetyllactosamine type. The enzyme appears to highly prefer the galactose residue at the Gal beta 1----4GlcNAc beta 1----2Man alpha 1----3 branch for attachment of the 1st mol of sialic acid in all the acceptors tested. The 2nd mol of sialic acid becomes linked mainly to the Gal beta 1----4GlcNAc beta 1----2Man alpha 1----6 branch in bi- and triantennary substrates, but this reaction invariably proceeds at a much lower rate. Under the conditions employed, the Gal beta 1----4GlcNAc beta 1----6Man alpha 1----6 branch is extremely resistant to alpha 2----6-sialylation. A higher degree of branching of the acceptors leads to a decrease in the rate of sialylation. In particular, the presence of the Gal beta 1----4GlcNAc beta 1----6Man alpha 1----6 branch strongly inhibits the rate of transfer of both the 1st and the 2nd mol of sialic acid. In addition, it directs the incorporation of the 2nd mol into tetraantennary structures toward the Gal beta 1----4GlcNAc beta 1----4Man alpha 1----3 branch. In contrast, the presence of the Gal beta 1----4GlcNAc beta 1----4Man alpha 1----3 branch has only minor effects on the rates of sialylation and, consequently, on the branch preference of sialic acid attachment. Results obtained with partial structures of tetraantennary acceptors indicate that the Man beta 1----4GlcNAc part of the core is essential for the expression of branch specificity of the sialyltransferase. The sialylation patterns observed in vivo in glycoproteins of different origin are consistent with the in vitro preference of alpha 2----6-sialyltransferase for the Gal beta 1----4GlcNAc beta 1----2Man alpha 1----3 branch. Our findings suggest that the terminal structures of branched glycans of the N-acetyllactosamine type are the result of the complementary branch specificity of the various glycosyltransferases that are specific for the acceptor sequence Gal beta 1----4GlcNAc-R.
Adrenocorticotropic Hormone Secretion in Rats Induced by Stimulation with Serotonergic Compounds (1999)

The serotonin receptors involved in the secretion of adrenocorticotropin hormone (ACTH) were investigated in conscious adult male rats. Administration of serotonin (5-HT), 5-hydroxytryptophan (5-HTP) in combination with the serotonin reuptake inhibitor fluoxetine (Flx), or of the 5-HT agonists 8-OH-DPAT (5-HT1A), 5-carboxamido-tryptamine (5-HT1A+1B+5A+7), RU 24969 (5-HT1B+1A), DOI (5-HT2A+2c), S-alpha-methyl-5-HT (5-HT2A+2B+2c), MK212 (5-HT2B+2c), or methyl-chlorophenyl-piperazine (5-HT2A+2c) dose-dependently stimulated ACTH secretion. The 5-HT3 agonist 2-methyl-5-HT had no effect. Administration of a 5-HT1 agonist in combination with any of the 5-HT2 agonists DOI, S-alpha-methyl-5-HT or MK212 had an additive effect on the plasma concentration of ACTH. The ACTH stimulating effect of each of the 5-HT agonists was inhibited by pretreatment with antagonists with corresponding 5-HT receptor affinity. The ACTH response to 5-HT or 5-HTP/Flx was inhibited by injection with the 5-HT1A+2A+2c+5A+7 antagonist methysergide, the 5-HT2A antagonist ketanserine and the 5-HT2C+2A antagonist LY 53857. The 5-HT1A antagonist WAY 100635 enhanced 5-HT- and 5-HTP/Flx-induced ACTH secretion, suggesting a presynaptic 5-HT1A autoreceptor effect of the drug. The 5-HT3 antagonist ondansetrone had no effect on the either of the 5-HT agonists. The 5-HT3+4 antagonist tropisetrone attenuated the effect of 5-HTP/Flx, which may suggest a stimulation of ACTH secretion via 5-HT4 receptors. It is concluded that 5-HT1A, 5-HT2A+2C, and to a lesser extent 5-HT1B receptors, but not 5-HT3 receptors are involved in the effects of serotonin agonists on ACTH secretion. Furthermore, an involvement of the 5-HT5A and the 5-HT7 receptor is possible.
Monoclonal Antibodies Against Human Cancer Stem Cells (2014)

Cancer stem cells (CSCs) are a subpopulation of tumor cells that display self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of cancer cells that comprise the tumor. CSCs exhibit intrinsic mechanisms of resistance to modern cancer therapeutics, allowing them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Various cell surface and transmembrane proteins expressed by CSCs, including CD44, CD47, CD123, EpCAM (CD326), CD133, IGF receptor I, and proteins of the Notch and Wnt signaling pathways have been identified. Recently, monoclonal antibodies and antibody constructs raised against these CSC proteins have shown efficacy against CSCs in human cancer xenograft mice, and some of them have demonstrated antitumor activity in clinical studies. Since current cancer therapies fail to eliminate CSCs, leading to cancer recurrence and progression, selective targeting of CSCs with monoclonal antibodies and antibody constructs may represent a novel therapeutic strategy against cancer.
Visualization of Synaptic Inhibition with an Optogenetic Sensor Developed by Cell-Free Protein Engineering Automation (2013)

We describe an engineered fluorescent optogenetic sensor, SuperClomeleon, that robustly detects inhibitory synaptic activity in single, cultured mouse neurons by reporting intracellular chloride changes produced by exogenous GABA or inhibitory synaptic activity. Using a cell-free protein engineering automation methodology that bypasses gene cloning, we iteratively constructed, produced, and assayed hundreds of mutations in binding-site residues to identify improvements in Clomeleon, a first-generation, suboptimal sensor. Structural analysis revealed that these improvements involve halide contacts and distant side chain rearrangements. The development of optogenetic sensors that respond to neural activity enables cellular tracking of neural activity using optical, rather than electrophysiological, signals. Construction of such sensors using in vitro protein engineering establishes a powerful approach for developing new probes for brain imaging.
Intrauterine pressure, ischemia markers, and experienced pain during administration of a vasopressin V1a receptor antagonist in spontaneous and vasopressin‐induced dysmenorrhea (2006)

Atosiban reduces vasopressin-induced intrauterine pressure in both healthy volunteers and dysmenorrheics, and reported pain in subjects with dysmenorrhea. The ischemia markers are not a useful biomarker index in women with dysmenorrhea. The dysmenorrhea pain evoked by vasopressin correlated poorly with area under the curve, which may suggest that the effect is mediated by more than one V1a-like receptor. We conclude that this model with recordings in healthy women is useful in the evaluation of drug candidates for primary dysmenorrhea.
Phage Display in Proteolysis and Signal Transduction (1999)

The power of the phage display technology relies on the coupling of the functional display of combinatorial peptide or protein libraries with the ability of each member in the library to self-replicate and, at the same time, to encode the primary structure of the displayed polypeptide in its genome. Phage display systems, therefore, reflect the principle of encoded combinatorial chemistry close to perfection. Phage display libraries have extensively been used for the selection of peptides, antibody combining sites or protein variants binding to given structures such as polypeptides, carbohydrates, nucleic acids or small molecular weight compounds. The use of peptide libraries in selecting molecular interaction partners was extensively described in numerous publications and was subject to a variety of review articles in the past. More recently, and in the focus of this review, combinatorial phage libraries have been employed to examine substrate recognition in catalysis and signal transduction. The sensitivity and versatility of phage display for probing molecular recognition and catalysis by enzymes was demonstrated inasmuch as discriminating peptide substrates could be identified for even closely related proteases or tyrosine kinases. Furthermore, the modification of whole phage libraries by tyrosine kinases led to the identification of phosphopeptides specific for Src-homology-2 (SH2)- and phosphotyrosine-binding (PTB) domains, which are both structural and functional modules facilitating substrate recognition by protein kinases, phosphatases or adapter molecules involved in signal transduction.
Defects in Macrophage Recruitment and Host Defense in Mice Lacking the CCR2 Chemokine Receptor (1997)

Chemokines are a structurally related family of cytokines that are important for leukocyte trafficking. The C-C chemokine monocyte chemoattractant protein-1 (MCP-1) is a potent monocyte activator in vitro and has been associated with monocytic infiltration in several inflammatory diseases. One C-C chemokine receptor, CCR2, has been identified that mediates in vitro responses to MCP-1 and its close structural homologues. CCR2 has also recently been demonstrated to be a fusion cofactor for several HIV isolates. To investigate the normal physiological function of CCR2, we generated mice with a targeted disruption of the ccr2 gene. Mice deficient for CCR2 developed normally and had no hematopoietic abnormalities. However, ccr2(-/-) mice failed to recruit macrophages in an experimental peritoneal inflammation model. In addition, these mice were unable to clear infection by the intracellular bacteria, Listeria monocytogenes. These results suggest that CCR2 has a nonredundant role as a major mediator of macrophage recruitment and host defense against bacterial pathogens and that MCP-1 and other CCR2 ligands are effectors of those functions.
Immunogenicity after one, two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto, South Africa (2002)

A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.
The Group A Streptococcal Carrier State (1988)

Streptococcal infection usually is defined as a positive throat culture with a serologic response to group A beta-hemolytic streptococci, and a patient with a positive throat culture and no serologic response is a streptococcal carrier. Studies suggest that streptococcal carriers should show little clinical response to antibiotic therapy when compared with patients with true streptococcal infections. Patients with acute pharyngitis were divided into three groups: group 1--38 patients with negative throat cultures; group 2--72 patients with a positive throat culture and a significant rise in streptococcal antibody titers; and group 3--77 patients with positive throat cultures and no significant rise in streptococcal antibody titers. Patients in group 2 and group 3 had a comparable and dramatic clinical response to antibiotic therapy that was considerably greater than the clinical response in the patients in group 1. These findings raise questions about the appropriateness of using streptococcal antibody responses to distinguish between the streptococcal carrier state and a true streptococcal infection.
Breast Conservation Therapy with Tumor Bed Irradiation Alone in a Selected Group of Patients with Stage I Breast Cancer (2001)

Radiotherapy after breast-conserving surgery increases local control. We tested the feasibility of limited surgery with tumor bed irradiation only with 192Ir in a selected group of patients with stage I breast cancer. Twenty-five breasts in 24 women more than 60 years old with low- or intermediate-grade stage I tumors were treated with placement of interstitial catheters at the time of lumpectomy and axillary node dissection. This procedure was followed by after-loading with low-dose 192Ir to deliver 20-25 Gy to the tumor bed over 24-48 hours. There were neither local recurrences in the breast nor distant recurrences at a median follow-up of 47 months (range 25-90 months). Cosmetic appearance ranged from very good to excellent. There were no long-term complications. It is feasible to treat a select group of patients with tumor bed irradiation, using relatively low doses of interstitial irradiation, with excellent local control and no significant morbidity.
World‐wide web: the information universe (2010)

Purpose The World‐Wide Web (W 3 ) initiative is a practical project designed to bring a global information universe into existence using available technology. This paper seeks to describe the aims, data model, and protocols needed to implement the “web” and to compare them with various contemporary systems. Design/methodology/approach Since Vannevar Bush's article, men have dreamed of extending their intellect by making their collective knowledge available to each individual by using machines. Computers provide us two practical techniques for human‐knowledge interface. One is hypertext, in which links between pieces of text (or other media) mimic human association of ideas. The other is text retrieval, which allows associations to be deduced from the content of text. The W 3 ideal world allows both operations and provides access from any browsing platform. Findings Various server gateways to other information systems have been produced, and the total amount of information available on the web is becoming very significant, especially since it includes all anonymous FTP archives, WAIS servers, and Gopher servers as well as specific W 3 servers. Originality/value The paper notices that a W 3 server could provide the functions of each of these servers, and so it looks forward to a single protocol that can be used by the whole community.
In Vitro Evolution and Selection of Proteins: Ribosome Display for Larger Libraries (1998)

The cell-free production of large protein libraries can now be achieved with the ribosome display technique. The use of intact ribosomes (R) in the translation of a mRNA library enables the rapid selection of the generated proteins (P) according to their affinity to a given immobilized binding partner (B).
How an exonuclease decides where to stop in trimming of nucleic acids: crystal structures of RNase T–product complexes (2012)

Exonucleases are key enzymes in the maintenance of genome stability, processing of immature RNA precursors and degradation of unnecessary nucleic acids. However, it remains unclear how exonucleases digest nucleic acids to generate correct end products for next-step processing. Here we show how the exonuclease RNase T stops its trimming precisely. The crystal structures of RNase T in complex with a stem-loop DNA, a GG dinucleotide and single-stranded DNA with different 3'-end sequences demonstrate why a duplex with a short 3'-overhang, a dinucleotide and a ssDNA with a 3'-end C cannot be further digested by RNase T. Several hydrophobic residues in RNase T change their conformation upon substrate binding and induce an active or inactive conformation in the active site that construct a precise machine to determine which substrate should be digested based on its sequence, length and structure. These studies thus provide mechanistic insights into how RNase T prevents over digestion of its various substrates, and the results can be extrapolated to the thousands of members of the DEDDh family of exonucleases.
The Fusion Glycoproteins of Human Respiratory Syncytial Virus of Subgroups A and B: Sequence Conservation Provides a Structural Basis for Antigenic Relatedness (1988)

Two major antigenic subgroups (A and B) have been described for human respiratory syncytial virus. The complete nucleotide sequence was determined for the fusion (F) mRNA of the subgroup B strain 18537 and the amino acid sequence of the F protein deduced, for comparison with the previously described sequences for the A2 strain of subgroup A. The F proteins (excluding the cleaved signal peptide) were 91% identical between the subgroups, consistent with the previously described high degree of antigenic relatedness. The greatest divergence occurred within the F2 subunit immediately preceding the cleavage activation site.
Control of aggregation in protein refolding: A variety of surfactants promote renaturation of carbonic anhydrase II (1995)

The denaturation and renaturation of carbonic anhydrase II (CAII) has been studied in several laboratories. Both thermodynamic and kinetic evidence support the existence of at least two intermediates between denatured and native protein. Previous studies have shown that on rapid dilution of a CAII solution from 5 M to 1 M guanidinium chloride, aggregation strongly competes with renaturation at higher protein concentrations, suggesting an upper limit for [CAII] of approximately 0.1%. Our experiments show 60% renaturation at 0.4% [CAII] and that aggregate formation is partially reversible. This yield can be substantially increased by several surfactant additives, including simple alkanols as well as micelle-forming surfactants. Effective surfactants (promoters) act by suppressing initial aggregate formation, not by dissolving aggregates. Promoters act on either the first folding intermediate (I1) or oligomers thereof. Eight of the 18 surfactants examined showed promoter activity, and no correlation was evident between promoter activity and chemical structure or surface tension lowering. These results indicate discrimination (molecular recognition) by I1 and/or its oligomers.
Matriptase-2, a Membrane-bound Mosaic Serine Proteinase Predominantly Expressed in Human Liver and Showing Degrading Activity against Extracellular Matrix Proteins (2002)

We have identified and cloned a fetal liver cDNA encoding a new serine proteinase that has been called matriptase-2. This protein exhibits a domain organization similar to other members of an emerging family of membrane-bound serine proteinases known as type II transmembrane serine proteinases. Matriptase-2 contains a short cytoplasmic domain, a type II transmembrane sequence, a central region with several modular structural domains including two CUB (complement factor C1s/C1r, urchin embryonic growth factor, bone morphogenetic protein) domains and three low density lipoprotein receptor tandem repeats, and finally, a C-terminal catalytic domain with all typical features of serine proteinases. The human matriptase-2 gene maps to 22q12-q13, a location that differs from all type II transmembrane serine proteinase genes mapped to date. Immunofluorescence and Western blot analysis of COS-7 cells transfected with the isolated cDNA confirmed that matriptase-2 is anchored to the cell surface. Matriptase-2 was expressed in Escherichia coli, and the purified recombinant protein hydrolyzed synthetic substrates used for assaying serine proteinases and endogenous proteins such as type I collagen, fibronectin, and fibrinogen. Matriptase-2 could also activate single-chain urokinase plasminogen activator, albeit with low efficiency. These activities were abolished by inhibitors of serine proteinases but not by inhibitors of other classes of proteolytic enzymes. Northern blot analysis demonstrated that matriptase-2 transcripts are only detected at significant levels in both fetal and adult liver, suggesting that this novel serine proteinase may play a specialized role in matrix remodeling processes taking place in this tissue during development or in adult tissues.
Compressed sensing for practical optical imaging systems: a tutorial (2011)

The emerging field of compressed sensing has potentially powerful implications for the design of optical imaging devices. In particular, compressed sensing theory suggests that one can recover a scene at a higher resolution than is dictated by the pitch of the focal plane array. This rather remarkable result comes with some important caveats however, especially when practical issues associated with physical implementation are taken into account. This tutorial discusses compressed sensing in the context of optical imaging devices, emphasizing the practical hurdles related to building such devices, and offering suggestions for overcoming these hurdles. Examples and analysis specifically related to infrared imaging highlight the challenges associated with large format focal plane arrays and how these challenges can be mitigated using compressed sensing ideas.
The Yeast SEN3 Gene Encodes a Regulatory Subunit of the 26S Proteasome Complex Required for Ubiquitin-Dependent Protein Degradation In Vivo (1995)

The yeast Sen1 protein was discovered by virtue of its role in tRNA splicing in vitro. To help determine the role of Sen1 in vivo, we attempted to overexpress the protein in yeast cells. However, cells with a high-copy SEN1-bearing plasmid, although expressing elevated amounts of SEN1 mRNA, show little increase in the level of the encoded protein, indicating that a posttranscriptional mechanism limits SEN1 expression. This control depends on an amino-terminal element of Sen1. Using a genetic selection for mutants with increased expression of Sen1-derived fusion proteins, we identified mutations in a novel gene, designated SEN3. SEN3 is essential and encodes a 945-residue protein with sequence similarity to a subunit of an activator of the 20S proteasome from bovine erythrocytes, called PA700. Earlier work indicated that the 20S proteasome associates with a multisubunit regulatory factor, resulting in a 26S proteasome complex that degrades substrates of the ubiquitin system. Mutant sen3-1 cells have severe defects in the degradation of such substrates and accumulate ubiquitin-protein conjugates. Most importantly, we show biochemically that Sen3 is a subunit of the 26S proteasome. These data provide evidence for the involvement of the 26S proteasome in the degradation of ubiquitinated proteins in vivo and for a close relationship between PA700 and the regulatory complexes within the 26S proteasome, and they directly demonstrate that Sen3 is a component of the yeast 26S proteasome.