gebhart/patrepeval huggingface dataset:
Constitutive Activation of Mitogen-activated Protein Kinase-activated Protein Kinase 2 by Mutation of Phosphorylation Sites and an A-helix Motif (1995)

A recently described downstream target of mitogen-activated protein kinases (MAPKs) is the MAPK-activated protein (MAPKAP) kinase 2 which has been shown to be responsible for small heat shock protein phosphorylation. We have analyzed the mechanism of MAPKAP kinase 2 activation by MAPK phosphorylation using a recombinant MAPKAP kinase 2-fusion protein, p44MAPK and p38/40MAPK in vitro and using an epitope-tagged MAPKAP kinase 2 in heat-shocked NIH 3T3 cells. It is demonstrated that, in addition to the known phosphorylation of the threonine residue carboxyl-terminal to the catalytic domain, Thr-317, activation of MAPKAP kinase 2 in vitro and in vivo is dependent on phosphorylation of a second threonine residue, Thr-205, which is located within the catalytic domain and which is highly conserved in several protein kinases. Constitutive activation of MAPKAP kinase 2 is obtained by replacement of both of these threonine residues by glutamic acid. A constitutively active form of MAPKAP kinase 2 is also obtained by deletion of a carboxyl-terminal region containing Thr-317 and the A-helix motif or by replacing the conserved residues of the A-helix. These data suggest a dual mechanism of MAPKAP kinase 2 activation by phosphorylation of Thr-205 inside the catalytic domain and by phosphorylation of Thr-317 outside the catalytic domain involving an autoinhibitory A-helix motif.
Expression, stability, and membrane integration of truncation mutants of bovine rhodopsin (1997)

Premature termination of protein synthesis by nonsense mutations is at the molecular origin of a number of inherited disorders in the family of G protein-coupled seven-helix receptor proteins. To understand how such truncated polypeptides are processed by the cell, we have carried out COS-1 cell expression studies of mutants of bovine rhodopsin truncated at the first 1, 1.5, 2, 3, or 5 transmembrane segments (TMS) of the seven present in wild-type opsin. Our experiments show that successful completion of different stages in the cellular processing of the protein [membrane insertion, N-linked glycosylation, stability to proteolytic degradation, and transport from the endoplasmic reticulum (ER) membrane] requires progressively longer lengths of the polypeptide chain. Thus, none of the truncations affected the ability of the polypeptides to be integral membrane proteins. C-terminal truncations that generated polypeptides with fewer than two TMS resulted in misorientation and prevented glycosylation at the N terminus, whereas truncations that generated polypeptides with fewer than five TMS greatly destabilized the protein. However, all of the truncations prevented exit of the polypeptide from the ER. We conclude that during the biogenesis of rhodopsin, proper integration into the ER membrane occurs only after the synthesis of at least two TMS is completed. Synthesis of the next three TMS confers a gradual increase in stability, whereas the presence of more than five TMS is necessary for exit from the ER.
The Predictive Parameters of Erythropoietin Hyporesponsiveness in Patients on Continuous Ambulatory Peritoneal Dialysis (2001)

These results indicate that CRP is the most important predictor of epoetin hyporesponsiveness.
Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II‐dependent pathway for antigen presentation (2008)

Some pathogenic bacteria form thick capsules that both block immune responses through inhibition of complement deposition and phagocytosis and stimulate a weak response resulting from a lack of T-cell involvement. Contrary to this model, capsular polysaccharides from 23 serotypes of Streptococcus pneumoniae have been successfully used in a multivalent vaccine in the absence of a carrier protein. Furthermore, type I pneumococcal polysaccharide (Sp1) has been shown to activate T cells in vivo and in vitro via an uncharacterized mechanism. In the present report, we demonstrate that Sp1 utilizes the major histocompatibility complex (MHC) class II pathway in antigen-presenting cells (APCs) for processing and presentation. APCs internalize and process Sp1 through a nitric oxide-dependent mechanism and, once inside the cell, it associates with MHC II proteins in an H-2M-dependent manner that leads to in vivo T-cell activation. These results establish that Sp1 activates T cells which can lead to abscess formation in mice through an H-2M-dependent polysaccharide antigen presentation pathway in APCs, potentially contributing to pneumococcal polysaccharide vaccine efficacy through the recruitment of T-cell help.
Protein II* Influences Ferrichrome-iron Transport in Escherichia coli k12 (1979)

Ferrichrome-promoted iron uptake in Escherichia coli K12 is strictly dependent upon the tonA gene product, a 'minor' outer membrane protein. By selection for mutants of E. coli resistant to phages which require 'major' outer membrane proteins as receptors, strains with pronounced protein deficiencies were constructed. Such strains were tested for anomalous behaviour of ferrichrome transport. No significant differences in iron uptake were detected in E. coli K12 strains with markedly reduced amounts of protein I. However, a reduction in the initial velocity (up to 40%) was observed in E. coli deficient in outer membrane protein II. This difference was only evident when cells were grown under iron-starvation conditions; it was abolished when cells were grown in rich medium. Kinetic parameters for ferrichrome transport were determined for maximum velocity but for Km; double reciprocal plots showed a biphasic nature, probably attributable to a limited number of outer membrane binding sites and to the multi-component nature of the ferrichrome-iron transport system.
Parallel-program transformation using a metalanguage (1991)

Article Free Access Share on Parallel-program transformation using a metalanguage Authors: J. Allan Yang View Profile , Young-il Choo View Profile Authors Info & Claims PPOPP '91: Proceedings of the third ACM SIGPLAN symposium on Principles and practice of parallel programmingApril 1991 Pages 11–20https://doi.org/10.1145/109625.109628Published:01 April 1991Publication History 10citation2,955DownloadsMetricsTotal Citations10Total Downloads2,955Last 12 Months18Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Targeting of cytotoxic cells against tumors with heterocrosslinked, bispecific antibodies. (1988)

Cytotoxic cells express specific receptors on their surfaces by which they distinguish altered or foreign cells from normal autologous cells. Recently, a method has been developed by which the natural recognition system of cytotoxic cells can be artificially manipulated, giving rise to cytotoxic cells of any desired specificity, including specificity against tumor and virally infected cells. The method for retargeting cytotoxic cells employs heterocrosslinked antibodies, in which one antibody is directed against the cytotoxic cell receptor (CCR) involved in lysis, while the second antibody is directed against a target cell structure, for example a tumor or viral antigen. By linking the CCR directly to the target cell, the heterocrosslinked antibodies promote the formation of effector: target conjugates and signal the cytotoxic cell to deliver a lethal hit. T cells can be targeted by heteroconjugates containing antibodies against components of the T cell receptor complex, e.g., Ti or CD3, while several types of antibody-dependent cellular cytotoxicity (ADCC) effector cells, including K/NK cells, macrophages, and neutrophils, are targeted using heteroconjugates containing antibodies against Fc gamma receptors. In peripheral blood from normal donors at least six types of targetable activities have been identified in vitro. In Winn type tumor neutralization assays in nude mice, targeted T and K cells can prevent the establishment of subcutaneous tumor at low effector: tumor ratios. Moreover, targeted human peripheral blood T cells cause the eradication of established intraperitoneal human ovarian carcinoma in nude mouse models. Targeted cytotoxic cells therefore hold great promise as a novel form of cancer immunotherapy in humans.
Condensations of Isatin with Acetone by the Knoevenagel Method1 (1933)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCondensations of Isatin with Acetone by the Knoevenagel Method1F. Braude and H. G. LindwallCite this: J. Am. Chem. Soc. 1933, 55, 1, 325–327Publication Date (Print):January 1, 1933Publication History Published online1 May 2002Published inissue 1 January 1933https://pubs.acs.org/doi/10.1021/ja01328a041https://doi.org/10.1021/ja01328a041research-articleACS PublicationsRequest reuse permissionsArticle Views802Altmetric-Citations34LEARN 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
Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. (1992)

We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone.
Chemoenzymatic synthesis of glycoconjugate polymers starting from nonreducing disaccharides (2004)

Abstract Here we report the chemoenzymatic synthesis and recognition function of glycoconjugate polymers carrying nonreducing disaccharides [α‐ D ‐glucopyranosyl‐(1‐1)‐α‐ D ‐glucopyranoside (trehalose) and α‐ D ‐galactopyranosyl‐(1‐1)‐α‐ D ‐glucopyranoside (Gal‐type trehalose)]. The lipase‐catalyzed esterification of the disaccharides with divinyl sebacate is completely selective at the primary Glc 6‐OH position of trehalose and at the Gal 6‐OH position of Gal‐type trehalose. The resultant vinyl esters can be polymerized to yield glycoconjugate polymers with poly(vinyl alcohol) backbones. The interactions of the glycoconjugate polymers with lectins (concanavalin A and Bandeiraera simplicifolia ) are amplified because of the glycocluster effect. The polymer carrying pendant α‐ D ‐galactopyranosyl‐(1‐1)‐α‐ D ‐glucopyranoside shows inhibition activity against Shiga toxin‐1 based on a stereochemical structure similar to that of globosyl Gb2 disaccharide. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4598–4606, 2004
Adventitia as a target for intravascular local drug delivery. (1996)

Adventitia as a target for intravascular local drug delivery
Paranemic Crossover DNA:  A Generalized Holliday Structure with Applications in Nanotechnology (2004)

Paranemic crossover (PX) DNA is a four-stranded coaxial DNA complex containing a central dyad axis that relates two flanking parallel double helices. The strands are held together exclusively by Watson-Crick base pairing. The key feature of the structure is that the two adjacent parallel DNA double helices form crossovers at every point possible. Hence, reciprocal crossover points flank the central dyad axis at every major or minor groove separation. This motif has been modeled and characterized in an oligonucleotide system; a minor groove separation of five nucleotide pairs and major groove separations of six, seven, or eight nucleotide pairs produce stable PX DNA molecules; a major groove separation of 9 nucleotide pairs is possible at low concentrations. Every strand undergoes a crossover every helical repeat (11, 12, 13, or 14 nucleotides), but the structural period of each strand corresponds to two helical repeats (22, 24, 26, or 28 nucleotides). Nondenaturing gel electrophoresis shows that the molecules are stable, forming well-behaved complexes. PX DNA can be produced from closed dumbbells, demonstrating that the molecule is paranemic. Ferguson analysis indicates that the molecules are similar in shape to DNA double crossover molecules. Circular dichroism spectra are consistent with B-form DNA. Thermal transition profiles suggest a premelting transition in each of the molecules. Hydroxyl radical autofootprinting analysis confirms that there is a crossover point at each of the positions expected in the secondary structure. These molecules are generalized Holliday junctions.
Telomeric DNA-protein interactions of Oxytricha macronuclear DNA. (1987)

Telomeres of Oxytricha macronuclear chromatin exist as discrete nonnucleosomal DNA-protein complexes, each of which encompasses the terminal 100-150 bp of a macronuclear DNA molecule. We have used chemical and nuclease footprinting to examine the internal structure of these telomeric complexes. Remarkably salt-stable DNA-protein interactions result in methylation-protection of specific guanine residues in the 3'-terminal T4G4T4G4 tail. The methylation pattern seen in vivo and in isolated macronuclei is reconstituted in vitro when purified 55-kD and 43-kD telomere proteins are added to purified macronuclear DNA. Very different interactions are observed between protein and DNA within the region approximately 45-135 bp from the 5' terminus. The DNase I cleavage pattern indicates that this DNA lies on the outside surface of protein but is not part of a nucleosome. Our data suggest that the telomeric complexes have two structural domains characterized by their dissimilar DNA-protein interactions. We propose that functionally equivalent telomeres from other organisms could be accommodated in a similar telomeric chromatin structure.
Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1 (1999)

Posttranslational modifications such as ubiquitination and phosphorylation play an important role in the regulation of cellular protein function. Homeodomain-interacting protein kinase 2 (HIPK2) is a member of the recently identified family of nuclear protein kinases that act as corepressors for homeodomain transcription factors. Here, we show that HIPK2 is regulated by a ubiquitin-like protein, SUMO-1. We demonstrate that HIPK2 localizes to nuclear speckles (dots) by means of a speckle-retention signal. This speckle-retention signal contains a domain that interacts with a mouse ubiquitin-like protein conjugating (E2) enzyme, mUBC9. In cultured cells, HIPK2 is covalently modified by SUMO-1, and the SUMO-1 modification of HIPK2 correlates with its localization to nuclear speckles (dots). Thus, our results provide firm evidence that the nuclear protein kinase HIPK2 can be covalently modified by SUMO-1, which directs its localization to nuclear speckles (dots).
National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (1992)

Compelling evidence exists that the atherosclerotic process begins in childhood and progresses slowly into adulthood, at which time it leads frequently to coronary heart disease (CHD), the major cause of death in the United States. Despite substantial success in reducing CHD mortality in the past two decades, the disease is still responsible for more than 500 000 deaths annually. About 20% of hospital discharges for acute CHD are for premature disease, ie, in patients younger than 55 years of age. Many of these adults have children who may have CHD risk factors that need attention. Estimates of the annual cost of CHD range from $41.5 to $56 billion. The Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (which appears as a supplement to this issue of the journal) reviews the evidence that atherosclerosis or its precursors begin in young people; that elevated cholesterol levels early in life play a role in the development of adult atherosclerosis; that eating patterns and genetics affect blood cholesterol levels and CHD risk; and that lowering levels in children and adolescents will be beneficial. Cholesterol is the focus of the report, but other risk factors for atherosclerosis and CHD may originate early in life and should be addressed as well. Specifically, cigarette smoking should be discouraged; hypertension should be identified and treated; obesity should be avoided or reduced; regular aerobic exercise should be encouraged; and diabetes mellitus should be diagnosed and treated. SIGNIFICANCE OF BLOOD CHOLESTEROL LEVELS IN CHILDHOOD AND ADOLESCENCE
Real-Time Interferometric Monitoring System for Exposure Controlled Projection Lithography (2011)

Stereolithography is an additive manufacturing process in which liquid photopolymer resin is cross-linked and converted to solid polymer with an ultraviolet light source. Exposure Controlled Projection Lithography (ECPL) is a stereolithographic process in which incident radiation, patterned by a dynamic mask, passes through a transparent substrate to cure a photopolymer layer that grows progressively from the substrate surface. In contrast to existing stereolithography techniques, this technique uses a gray-scale projected image, or alternatively a series of binary bit-map images, to produce a three-dimensional polymer object with the desired shape, and it can be used on either flat or curved substrates. Like most stereolithographic technologies, ECPL works in a unidirectional fashion. Calibration constants derived experimentally are fed to the software used to control the system. This unidirectional fabrication method does not, by itself, allow the system to compensate for minor variations, thereby limiting the overall accuracy of the process. We present here a simple, real-time monitoring system based on interferometry, which can be used to provide feedback control to the ECPL process, thus making it more robust and increasing system accuracy. The results obtained from this monitoring system provide a means to better visualize and understand the various phenomena occurring during the photopolymerization of transparent photopolymers.
Extemporaneous Compounding of Oral Liquid Dosage Formulations and Alternative Drug Delivery Methods for Anticancer Drugs (2011)

Oncology pharmacists face a constant challenge with patients who cannot swallow oral anticancer drugs, making extemporaneous oral liquid preparation a requirement. Improper extemporaneous preparation of these agents, especially with the traditional chemotherapy with a narrow therapeutic index, may increase the risk of over- or underdosing. In community pharmacies, multiple barriers exist that prevent these pharmacies from preparing extemporaneous oral anticancer drug formulations for a patient's use at home. In a home setting, patients or caregivers without proper counseling and education on how to safely handle chemotherapy are at increased risk for exposure to these drugs. Based on a review of the literature, compounding recipes are available for 46% of oral anticancer agents. A paucity of data exists on dose uniformity, bioequivalence, and stability of extemporaneous oral liquid formulations of anticancer drugs. Pharmacists must have an understanding of the basic scientific principles that are an essential foundation for the proper preparation of extemporaneous oral anticancer liquid formulations. The collaborative effort of a multidisciplinary team can also help identify different barriers in the community setting, especially in areas where community pharmacies may lack resources for the extemporaneous compounding of oral chemotherapy, and to find ways to coordinate better pharmaceutical care. There are great opportunities for oncology pharmacists, as well as community pharmacists, as a resource for educating and monitoring patients receiving oral chemotherapy to ensure dosing accuracy, safe administration, and proper disposal of hazardous drugs. Development of national guidelines to promote standards of practice in the community and/or home setting is urgently needed to help improve the safety of dispensing and handling oral chemotherapeutic agents, including extemporaneously compounded oral liquid formulations of these drugs.
The Effects of Normal as Compared with Low Hematocrit Values in Patients with Cardiac Disease Who Are Receiving Hemodialysis and Epoetin (1998)

In this randomized, prospective, open-label trial, we studied 1233 patients with congestive heart failure or ischemic heart disease who were undergoing hemodialysis at 51 centers (see the Appendix). The institutional review boards at all centers approved the protocol, and all the patients gave written, informed consent. All the patients had end-stage renal disease and were undergoing longterm hemodialysis, and they had hematocrit values of 27 to 33 percent while receiving epoetin during the four weeks before enrollment. Ninety percent of the patients received epoetin intrave-