gebhart/patrepeval huggingface dataset:
Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis (2001)

Several members of the Rubiaceae and Violaceae families produce a series of cyclotides or macrocyclic peptides of 29-31 amino acids with an embedded cystine knot. We aim to understand the mechanism of synthesis of cyclic peptides in plants and have isolated a cDNA clone that encodes the cyclotide kalata B1 as well as three other clones for related cyclotides from the African plant Oldenlandia affinis. The cDNA clones encode prepropeptides with a 20-aa signal sequence, an N-terminal prosequence of 46-68 amino acids and one, two, or three cyclotide domains separated by regions of about 25 aa. The corresponding cyclotides have been isolated from plant material, indicating that the cyclotide domains are excised and cyclized from all four predicted precursor proteins. The exact processing site is likely to lie on the N-terminal side of the strongly conserved GlyLeuPro or SerLeuPro sequence that flanks both sides of the cyclotide domain. Cyclotides have previously been assigned an antimicrobial function; here we describe a potent inhibitory effect on the growth and development of larvae from the Lepidopteran species Helicoverpa punctigera.
A Double-Blind Study Comparing the Effectiveness of Cromolyn Sodium and Sustained-Release Theophylline in Childhood Asthma (1984)

The effectiveness of cromolyn sodium and theophylline on asthma in children was compared during a 3-month trial. Forty-six children (aged 5 to 15 years) with asthma were assigned at random to cromolyn or theophylline (Theo-Dur) treatment groups. Each subject received theophylline placebo or cromolyn placebo in addition to the active drugs. A methacholine challenge test was done at the start of the study to document asthma and was repeated during the third month. The theophylline dosage was regulated to obtain serum levels of 10 to 15 micrograms/mL by a physician not involved directly with patient care. Forty patients completed the study. Both theophylline and cromolyn treatment groups showed improvement from base-line status in terms of symptom scores, pulmonary function, and decreased use of inhaled albuterol. Patients treated with theophylline had more side effects and required more frequent office visits than those treated with cromolyn. Both groups had decreased sensitivity to methacholine, and for one statistical test patients treated with cromolyn improved significantly. These results indicate that cromolyn is as effective as theophylline in treating mild to moderate asthma in children; additional benefits were fewer side effects and a possible decrease in bronchial hyperactivity.
All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae (1997)

The cyclophilins and FK506 binding proteins (FKBPs) bind to cyclosporin A, FK506, and rapamycin and mediate their immunosuppressive and toxic effects, but the physiological functions of these proteins are largely unknown. Cyclophilins and FKBPs are ubiquitous and highly conserved enzymes that catalyze peptidyl-prolyl isomerization, a rate-limiting step during in vitro protein folding. We have addressed their functions by a genetic approach in the yeast Saccharomyces cerevisiae. Five cyclophilins and three FKBPs previously were identified in yeast. We identified four additional enzymes: Cpr6 and Cpr7, which are homologs of mammalian cyclophilin 40 that have also recently been independently isolated by others, Cpr8, a homolog of the secretory pathway cyclophilin Cpr4, and Fpr4, a homolog of the nucleolar FKBP, Fpr3. None of the eight cyclophilins or four FKBPs were essential. Surprisingly, yeast mutants lacking all 12 immunophilins were viable, and the phenotype of the dodecuplet mutant resulted from simple addition of the subtle phenotypes of each individual mutation. We conclude that cyclophilins and FKBPs do not play an essential general role in protein folding and find little evidence of functional overlap between the different enzymes. We propose that each cyclophilin and FKBP instead regulates a restricted number of unique partner proteins that remain to be identified.
Helium bubble and blister formation for Ni and an amorphous Fe-Ni-Mo-B alloy during 5 keV implantation at 300 K (1982)

Abstract Results are presented for helium bubble formation in Ni and amorphous Fe40Ni38Mo4Bl8 during 5 keV He-implantation at 300 K. The formation of helium blisters on the surface is also reported.
Tn 5 /IS 50 target recognition (1998)

This communication reports an analysis of Tn5/IS50 target site selection by using an extensive collection of Tn5 and IS50 insertions in two relatively small regions of DNA (less than 1 kb each). For both regions data were collected resulting from in vitro and in vivo transposition events. Since the data sets are consistent and transposase was the only protein present in vitro, this demonstrates that target selection is a property of only transposase. There appear to be two factors governing target selection. A target consensus sequence, which presumably reflects the target selection of individual pairs of Tn5/IS50 bound transposase protomers, was deduced by analyzing all insertion sites. The consensus Tn5/IS50 target site is A-GNTYWRANC-T. However, we observed that independent insertion sites tend to form groups of closely located insertions (clusters), and insertions very often were spaced in a 5-bp periodic fashion. This suggests that Tn5/IS50 target selection is facilitated by more than two transposase protomers binding to the DNA, and, thus, for a site to be a good target, the overlapping neighboring DNA should be a good target, too. Synthetic target sequences were designed and used to test and confirm this model.
Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor (2015)

Using lentiviral technology, we recently demonstrated that incorporation of CD27 costimulation into CARs greatly improves antitumor activity and T cell persistence. Still, virus-mediated gene transfer is expensive, laborious and enables long-term persistence, creating therapies which cannot be easily discontinued if toxic. To address these concerns, we utilized a non-integrating RNA platform to engineer human T cells to express FRα-specific, CD27 CARs and tested their capacity to eliminate human FRα(+) cancer. Novel CARs comprised of human components were constructed, C4-27z and C4opt-27z, a codon-optimized variant created for efficient expression. Following RNA electroporation, C4-27z and C4opt-27z CAR expression is initially ubiquitous but progressively declines across T cell populations. In addition, C4-27z and C4opt-27z RNA CAR T cells secrete high levels of Th-1 cytokines and display strong cytolytic function against human FRα(+) cancers in a time- and antigen-dependent manner. Further, C4-27z and C4opt-27z CAR T cells exhibit significant proliferation in vivo, facilitate the complete regression of fully disseminated human ovarian cancer xenografts in mice and reduce the progression of solid ovarian cancer. These results advocate for rapid progression of C4opt-27z RNA CAR to the clinic and establish a new paradigm for preclinical optimization and validation of RNA CAR candidates destined for clinical translation.
The PPP Encryption Control Protocol (ECP) (1996)

This document defines a method for negotiating data encryption over
PPP links. [STANDARDS-TRACK]
Genetically engineered antibodies for direct antineoplastic treatment and systematic delivery of various therapeutic agents to cancer cells (2001)

Classical antineoplastic therapeutic modalities such as surgery, radiation, and chemotherapy not only fail to cure the great majority of neoplasms, but their employment often leads to severe and debilitating side effects associated with severe neoplasm-related morbidity. Immunotherapy as a fourth modality of anti-cancer therapy has already been proven to be quite effective. The astonishing immunophenotypic (IP) heterogeneity of neoplastic cells, the different cytotoxic activity associated with the moiety linked to given monoclonal antibodies (mAb), and mostly the impressive genetic modulation capabilities of cancer cells still remain as yet unsolved difficulties in the present immunotherapy of human neoplasms. The advances in mAb production have revitalised the initial concept of use of cancer cell specific "magic bullets." Antibodies represent new approaches to anti-cancer therapy: they are neoplastic cell-specific and lethal to neoplastically transformed cells via immune effector mechanisms with no toxicity to normal tissues. They are being observed and developed, adhering to the old prayer: "Destroy the diseased tissues, preserve the normal." Strategies for the employment of antibodies include: 1) immune reaction directed destruction of neoplastic cells; 2) interference with the growth and differentiation of malignant cells; 3) antigen epitope directed transport of anti-cancer agents to neoplastic cells; 4) anti-idiotype tumour vaccines; and 5) development of engineered (humanized) mouse mAbs for anticancer therapy. In addition, a variety of agents (e.g. toxins, radionuclides, chemotherapeutic drugs) have been conjugated to mouse and human mAbs for selective delivery to neoplastic cells.
Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29 (1978)

The retrovirus strain MC29 induces a variety of tumors in chickens, including myelocytomatosis and carcinomas of the kidney and liver. In addition, the virus can transform cultures of embryonic avian macrophages and fibroblasts. We have characterized the genome of MC29 virus and have identified nucleotide sequences that may encode the oncogenic potential ofthe virus. MC29 virus can replicate only with the assistance of a related helper virus. The defect in replication is apparently a consequence of a deletion in one or more viral genes: the haploid genome of the MC29 virus has a molecular weight of ca. 1.7 X 10(6), whereas the genome of the helper virus MCAV has a molecular weight of ca. 3.1 X 10(6). Although MC29 virus transforms fibroblasts in culture, its genome has no detectable homology with the gene src that is responsible for transformation of fibroblasts by avian sarcoma viruses. We prepared radioactive single-stranded DNA complementary to nucleotide sequences present in the genome of MC29 virus but not in the genome of MCAV (cDNA(MC29)). If they are contiguous, these sequences (ca. 1,500 nucleotides) are sufficiently complex to encode at least one protein. Homologous sequences were not detectable in several strains of avian sarcoma viruses or in an endogenous virus of chickens. Our findings confirm and extend recent reports from other laboratories and lead to the conclusion that MC29 virus may contain a previously unidentified gene(s) that is capable of transforming several distinct target cells. The evolutionary origins of this putative gene and its location on the viral genome can be explored with cDNA(MC29).
Val216 decides the substrate specificity of α‐glucosidase in Saccharomyces cerevisiae (2004)

Differences in the substrate specificity of alpha-glucosidases should be due to the differences in the substrate binding and the catalytic domains of the enzymes. To elucidate such differences of enzymes hydrolyzing alpha-1,4- and alpha-1,6-glucosidic linkages, two alpha-glucosidases, maltase and isomaltase, from Saccharomyces cerevisiae were cloned and analyzed. The cloned yeast isomaltase and maltase consisted of 589 and 584 amino acid residues, respectively. There was 72.1% sequence identity with 165 amino acid alterations between the two alpha-glucosidases. These two alpha-glucosidase genes were subcloned into the pKP1500 expression vector and expressed in Escherichia coli. The purified alpha-glucosidases showed the same substrate specificities as those of their parent native glucosidases. Chimeric enzymes constructed from isomaltase by exchanging with maltase fragments were characterized by their substrate specificities. When the consensus region II, which is one of the four regions conserved in family 13 (alpha-amylase family), is replaced with the maltase type, the chimeric enzymes alter to hydrolyze maltose. Three amino acid residues in consensus region II were different in the two alpha-glucosidases. Thus, we modified Val216, Gly217, and Ser218 of isomaltase to the maltase-type amino acids by site-directed mutagenesis. The Val216 mutant was altered to hydrolyze both maltose and isomaltose but neither the Gly217 nor the Ser218 mutant changed their substrate specificity, indicating that Val216 is an important residue discriminating the alpha-1,4- and 1,6-glucosidic linkages of substrates.
Apolipoprotein A-I-cell membrane interaction: extracellular assembly of heterogeneous nascent HDL particles. (1993)

The ability of lipid-free human apoA-I expressed by transfected Chinese hamster ovary (CHO) cells to form apoA-I-lipid complexes extracellularly when incubated with CHO cell monolayers was investigated. Lipid-free apoA-I was incubated with nontransfected CHO-C19 cells for 24 h and extracellular assembly products were isolated at d < or = 1.235 g/ml; approximately 12% of the incubated apoA-I floated at d < or = 1.235 g/ml when apoA-I was added at 10 micrograms/ml. The composition of the particles was 51.3% protein, 20.3% phospholipid, and 28.3% cholesterol. Electron microscopy of the apoA-I-lipid complexes revealed that discoidal particles 15.4 +/- 4.1 nm diameter predominated but some vesicular particles 34.7 +/- 16.8 nm diameter were also in evidence. Nondenaturing gradient gel electrophoresis of the extracellular assembly products formed after 24 h incubation with 10 micrograms/ml apoA-I showed particle size heterogeneity with major bands at 11.2 and 9.0 nm; additional minor components banded at 7.3, 17.7, and 19.5 nm. This size distribution, as well as composition and electron microscopic structure, is similar to that of complexes isolated from the medium of CHO cells transfected with the human apoA-I gene. The formation of extracellular assembly complexes was concentration-dependent such that at 2 micrograms apoA-I/ml for 24 h, primarily 7.3 nm complexes were formed; at 4 micrograms/ml the distribution was more heterogeneous and the major band peaked at 9.2 nm, while at 8 micrograms/ml the 7.3 nm component was greatly diminished and the 11.2 nm component was the major one.(ABSTRACT TRUNCATED AT 250 WORDS)
DNA-Encoded Antibody Libraries:  A Unified Platform for Multiplexed Cell Sorting and Detection of Genes and Proteins (2007)

Whether for pathological examination or for fundamental biology studies, different classes of biomaterials and biomolecules are each measured from a different region of a typically heterogeneous tissue sample, thus introducing unavoidable sources of noise that are hard to quantitate. We describe the method of DNA-encoded antibody libraries (DEAL) for spatially multiplexed detection of ssDNAs and proteins as well as for cell sorting, all on the same diagnostic platform. DEAL is based upon the coupling of ssDNA oligomers onto antibodies which are then combined with the biological sample of interest. Spotted DNA arrays, which are found to inhibit biofouling, are utilized to spatially stratify the biomolecules or cells of interest. We demonstrate the DEAL technique for (1) the rapid detection of multiple proteins within a single microfluidic channel, and, with the additional step of electroless amplification of gold-nanoparticle labeled secondary antibodies, we establish a detection limit of 10 fM for the protein IL-2, 150 times more sensitive than the analogue ELISA; (2) the multiplexed, on-chip sorting of both immortalized cell lines and primary immune cells with an efficiency that exceeds surface-confined panning approaches; and (3) the co-detection of ssDNAs, proteins, and cell populations on the same platform.
Immune response gene products (Ia antigens) on glial and endothelial cells in virus-induced demyelination. (1987)

Theiler's murine encephalomyelitis virus induced central nervous system demyelination in susceptible strains of mice with s, q, v, p, and f H-2D alleles. We used immunoelectron microscopy to look for differential production of class II immune response gene products (Ia) within astrocytes, oligodendrocytes, microglia, and endothelial cells. Spinal cord sections from susceptible mice (B10.S and B10.ASR2) showed increased content of Ia in glial and endothelial cells. In contrast, resistant mice [B10.S(9R)] showed minimal Ia production within the CNS. The findings indicate an important role of class II immune response products on glial cells during demyelination after virus infection.
Bromine-Mediated Addition of Nucleophiles to the Electron-Rich Pyrimidine Subunit of Tirilazad (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBromine-Mediated Addition of Nucleophiles to the Electron-Rich Pyrimidine Subunit of TirilazadJohn E. Cabaj, Peter G. M. Wuts, and Kevin E. HenegarCite this: J. Org. Chem. 1994, 59, 17, 5090–5092Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://doi.org/10.1021/jo00096a068Request reuse permissionsArticle Views250Altmetric-Citations3LEARN 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 InReddit PDF (406 KB) Get e-Alertsclose Get e-Alerts
Therapy of bronchial asthma with adenosine receptor agonists or antagonists. (2001)

Adenosine is an endogenous nucleoside that is released under pathological conditions and interacts with four G-protein-coupled receptor subtypes. These receptors are widely distributed throughout the body. They are involved in many central and peripheral processes, including immunological and inflammatory responses. In inflammatory and asthmatic conditions, the extracellular concentration of adenosine increases in the airway tissue. It enhances mast cell degranulation and bronchoconstriction, but may also inhibit eosinophil or lymphocyte function or modulate reactive oxygen species generation in neutrophils. Despite a large number of studies clearly indicating the effects of adenosine in vitro, many aspects of the mechanisms involved in the adenosine-mediated responses are still unclear, and our knowledge is limited in understanding the complex multifactorial interactions occurring in the whole body. The discovery of adenosine receptor compounds acting with increasing selectivity will bring new approaches to the use of adenosine receptor agonists and antagonists and may clarify some of the current uncertainties. On the basis of our present knowledge, the development of adenosine A(2A)- or (A3)-receptor agonists as antiinflammatory agents or A(2B)-receptor antagonists as inhibitors of mast cell degranulation for the treatment of asthma holds promise.
Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in-vivo (2002)

Cationic liposomes bind with nucleic acids such as plasmids and oligodeoxynucleotides to form complexes known as lipoplexes. Although these lipoplexes have several advantages over other forms of nucleic acid transfer methods in cell culture and in-vivo, toxicity remains a problem, especially in-vivo. Nevertheless, these carriers have been used in clinical trials against cystic fibrosis and cancer and their usage is attributed mainly to their versatility, especially when it comes to the range of routes available for administration of nucleic-acid-based drugs in-vivo.
MR imaging of silicone gel–filled breast implants in vivo with a method that visualizes silicone selectively (1993)

The lack of an adequately sensitive method for detecting silicone leakage and reported serious complications due to silicone leakage were cited as justification by the U.S. Food and Drug Administration for imposing the current restrictions on silicone gel-filled breast prostheses. The authors report a new magnetic resonance imaging method for visualizing silicone leakage: the silicone-only sequence (SOS). The method uses the conventional STIR (short-inversion-time inversion-recovery) technique combined with a 1331 radio-frequency pulse train widely used for water suppression in spectroscopy. With the SOS, silicone can be imaged while signals from fat and water are suppressed. The authors used the SOS to image phantoms and normal and ruptured silicone gel-filled breast prostheses.
Inhibition of lysosomal α-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens (1980)

An indolizidine alkaloid (swainsonine) was isolated from the plant Swainsona canescens. Swainsonine is a specific and potent inhibitor of alpha-mannosidase (EC 3.2.1.24) and when administered to animals produces a phenocopy of the genetically based lysosomal storage disease, mannosidosis. Evidence is presented to suggest that swainsonine is a reversible active site-directed inhibitor of lysosomal alpha-mannosidase.
The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the human and mouse genomes (2009)

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.
Predominance of TH1 Response in Tumor-Bearing Mice and Cancer Patients Treated With AS 101 (1996)

Isolation and characterization of a distinct cytokine pattern in patients with advanced cancer treated with AS101 may contribute to the development of intervention strategies using this compound.