gebhart/patrepeval huggingface dataset:
Polypeptides from p-Phenylalanine Mustard1 (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolypeptides from p-Phenylalanine Mustard1Carol W. Mosher, Robert H. Iwamoto, Edward M. Acton, and Leon GoodmanCite this: J. Med. Chem. 1964, 7, 5, 650–652Publication Date (Print):September 1, 1964Publication History Published online1 May 2002Published inissue 1 September 1964https://doi.org/10.1021/jm00335a019RIGHTS & PERMISSIONSArticle Views56Altmetric-Citations5LEARN 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 (426 KB) Get e-Alerts Get e-Alerts
Reverse Transcriptase (EC 2.7.7.49): The Use of Cloned Maloney Murine Leukemia Virus Reverse Transcriptase to Synthesize DNA from RNA (2003)

The conversion of mRNA into cDNA is the essential first step in the study of eukaryotic cell products expressed from cloned genes. The key enzyme used first in this process, retroviral RNA-directed DNA polymerase (reverse transcriptase), catalyzes the synthesis of a DNA copy of an RNA template in the presence of a suitable primer. Reverse transcriptase (RT) was discovered in 1970 (,) and was first used to copy a eukaryotic cell mRNA in 1971 (, , ); the first cDNA clones prepared using RT were reported in 1976 (). Until recently, the only enzyme available was purified from avian myeloblastosis virus (AMV). The overall quality and consistency of commercially available AMV RT preparations have improved dramatically in the last six years, although considerable differences in performance characteristics still exist among enzyme preparations from different commercial suppliers (). In addition, parameters for carrying out first-strand cDNA synthesis from poly(A)+ mRNA populations with AMV RT have been optimized thoroughly (); standard optima exist for pH, nucleotide concentration, and monovalent and divalent cation concentration; also essential stimulatory additives (such as sodium pyrophosphate and spermidine-HCl) have been identified. Furthermore, conditions have been established for proper handling and storage of the enzyme.
Abstract A207: Utilizing human OX40 knock-in mice (HuGEMMTM) to assess antitumor efficacy of OX40-agonistic antibodies (2018)

Abstract OX40 is a costimulatory molecule of TNF receptor family, primarily expressed on activated effector T cells and regulatory T cells. Engagement of OX40 by ligand leads to dramatic expansion, effector function, cytokine production, and survival of T cells. Several OX40-agonistic antibodies are in early stages of clinical development and some have shown promising antitumor immunity and improved tumor-free survival in the patients compared with standard-of-care therapies. Preclinical studies using surrogate OX40-agonistic antibodies have also shown robust tumor growth inhibition (TGI) efficacies, especially when combined with other checkpoint inhibitors like PD1 and CTLA-4 antibodies. However, we are lacking reliable preclinical models to assess the efficacy of human therapeutic antibodies. To address this need, we created a human OX40 knock-in GEMM (OX40 HuGEMM), where the entire 2.5 Kb mouse OX40 coding region is replaced by human OX40. We confirmed the expression of human OX40 in the 95% of activated T cells from the homozygous knock-in mice, while the mouse OX40 is completely eliminated. In the heterozygous knock-in mice, 58% of activated T cells express both mouse and human OX40. We then used both heterozygous and homozygous knock-in mice for efficacy studies of OX40 antibodies. In the heterozygous knock-in mice bearing MC38 syngeneic tumors, human and mouse OX40 antibody monotherapies led to 49% and 20% TGI, respectively, while their combination with PD1 antibody was synergistically effective, resulting in ~90% TGI with multiple complete tumor regressions. When we grafted the homozygous knock-in mice with B16F10 syngeneic tumors, single 5 mg/kg dose of an investigational human OX40 antibody led to 47% TGI. Tumor-killing efficacy of OX40 antibody is also correlated with significantly increased tumor infiltrated T cells and NK cells. Taken together, our OX40 HuGEMM provides an urgently needed tool for testing in vivo efficacy of human OX40 therapeutics, both as a single agent and as various combination strategies with other treatment modalities. Citation Format: Xuesong Huang, Lei Zheng, Wenyi Ouyang, Mingkun Zhang, Annie Xiaoyu An, Jing Zhao, Xiang Gao, Jean Pierre Wery, Qian Shi. Utilizing human OX40 knock-in mice (HuGEMMTM) to assess antitumor efficacy of OX40-agonistic antibodies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A207.
Specific Binding Sites for an Antifungal Plant Defensin from Dahlia (Dahlia merckii) on Fungal Cells Are Required for Antifungal Activity (2000)

Dm-AMP1, an antifungal plant defensin from seeds of dahlia (Dahlia merckii), was radioactively labeled with t-butoxycarbonyl-[35S]-L-methionine N-hydroxy-succinimi-dylester. This procedure yielded a 35S-labeled peptide with unaltered antifungal activity. [35S]Dm-AMP1 was used to assess binding on living cells of the filamentous fungus Neurospora crassa and the unicellular fungus Saccharomyces cerevisiae. Binding of [35S]Dm-AMP1 to fungal cells was saturable and could be competed for by preincubation with excess, unlabeled Dm-AMP1 as well as with Ah-AMP1 and Ct-AMP1, two plant defensins that are highly homologous to Dm-AMP1. In contrast, binding could not be competed for by more distantly related plant defensins or structurally unrelated antimicrobial peptides. Binding of [35S]Dm-AMP1 to either N. crassa or S. cerevisiae cells was apparently irreversible. In addition, whole cells and microsomal membrane fractions from two independently obtained S. cerevisiae mutants selected for resistance to Dm-AMP1 exhibited severely reduced binding affinity for [35S]Dm-AMP1, compared with wild-type yeast. This finding suggests that binding of Dm-AMP1 to S. cerevisiae plasma membranes is required for antifungal activity of this protein.
Negative enrichment by immunomagnetic nanobeads for unbiased characterization of circulating tumor cells from peripheral blood of cancer patients (2011)

Enriching CTCs using CD45 depletion allowed for detection of epithelial cancer cells not displaying the classical phenotype. This potentially leads to a more accurate estimation of the number of CTCs. If detection of CTCs without a classical epithelial phenotype has clinical relevance need to be determined.
Force Sensing Robot Fingers using Embedded Fiber Bragg Grating Sensors and Shape Deposition Manufacturing (2007)

Force sensing is an essential requirement for dexterous robot manipulation. Although strain gages have been widely used, a new sensing approach is desirable for applications that require greater robustness, design flexibility and immunity to electromagnetic noise. An exoskeletal force sensing robot finger was developed by embedding fiber Bragg grating (FBG) sensors into a polymer-based structure. Multiple FBG sensors were embedded into the structure to allow the manipulator to sense and measure both contact forces and grasping forces. In order to fabricate a three-dimensional structure, a new shape deposition manufacturing (SDM) process was explored. The sensorized SDM-fabricated finger was then characterized using an FBG interrogator. A force localization scheme is also described
Covalent HLA-B27/peptide complex induced by specific recognition of an aziridine mimic of arginine. (1996)

The class I major histocompatibility complex (MHC) glycoprotein HLA-B27 binds short peptides containing arginine at peptide position 2 (P2). The HLA-B27/peptide complex is recognized by T cells both as part of the development of the repertoire of T cells in the cellular immune system and during activation of cytotoxic T cells. Based on the three-dimensional structure of HLA-B27, we have synthesized a ligand with an aziridine-containing side chain designed to mimic arginine and to bind covalently in the arginine-specific P2 pocket of HLA-B27. Using tryptic digestion followed by mass spectrometry and amino acid sequencing, the aziridine-containing ligand is shown to alkylate specifically cysteine 67 of HLA-B27. Neither free cysteine in solution nor an exposed cysteine on a class II MHC molecule can be alkylated, showing that specific recognition between the anchor side-chain pocket of an MHC class I protein and the designed ligand (propinquity) is necessary to induce the selective covalent reaction with the MHC class I molecule.
Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action. (1998)

Platelet microbicidal proteins (PMPs) are hypothesized to exert microbicidal effects via cytoplasmic membrane disruption. Transmission electron microscopy demonstrated a temporal association between PMP exposure, damage of the Staphylococcus aureus cytoplasmic membrane ultrastructure, and subsequent cell death. To investigate the mechanisms of action of PMPs leading to membrane damage, we used flow cytometry to compare the effects of two distinct PMPs (thrombin-induced PMP-1 [tPMP-1] or PMP-2) with human neutrophil defensin-1 (hNP-1) on transmembrane potential (Deltapsi), membrane permeabilization, and killing of S. aureus. Related strains 6850 (Deltapsi -150 mV) and JB-1 (Deltapsi -100 mV; a respiration-deficient menadione auxotroph of 6850) were used to assess the influence of Deltapsi on peptide microbicidal effects. Propidium iodide (PI) uptake was used to detect membrane permeabilization, retention of 3,3'-dipentyloxacarbocyanine (DiOC5) was used to monitor membrane depolarization (Deltapsi), and quantitative culture or acridine orange accumulation was used to measure viability. PMP-2 rapidly depolarized and permeabilized strain 6850, with the extent of permeabilization inversely related to pH. tPMP-1 failed to depolarize strain 6850, but did permeabilize this strain in a manner directly related to pH. Depolarization, permeabilization, and killing of strain JB-1 due to PMPs were significantly less than in strain 6850. Growth in menadione reconstituted Deltapsi of JB-1 to a level equivalent to 6850, and was associated with greater depolarization due to PMP-2, but not tPMP-1. Reconstitution of Deltapsi also enhanced permeabilization and killing of JB-1 due to tPMP-1 or PMP-2. Both PMP-2 and tPMP-1 caused significant reductions in viability of strain 6850. In contrast to tPMP-1 or PMP-2, defensin hNP-1 depolarized, permeabilized, and killed both strains 6850 and JB-1 equally, and in a manner directly related to pH. Collectively, these data indicate that membrane dysfunction and cell death due to tPMP-1, PMP-2, or hNP-1 likely involve different mechanisms. These findings may also reveal new insights into the microbicidal activities versus mammalian cell toxicities of antimicrobial peptides.
Application of Mesenchymal Stem Cell in Immunotherapy——Review (2005)

There has been an increasing interest in recent years on mesenchymal stem cell (MSC). It is well known that MSCs are capable of self-renewal and differentiating into many cell lineages. MSC can be expended to a large quantity that is required for clinical transplantation. Recent studies show that MSC have potential application in immune diseases due to their unique immunologic characteristics, such as low immunogenicity and immunoregulatory function. But their immunoregulatory mechanism is not yet clear. This review discusses the advances in researches on the mechanism of MSCs′ immunoregulatory function and potential clinical application in immune disease and organ transplantation.
Expression of cartilage extracellular matrix and potential regulatory genes in a new human chondrosarcoma cell line (1998)

A human chondrosarcoma cell line has been established from an aggressive chondrosarcoma. The cells grow in a monolayer culture (doubling time: 2 days) and form aggregates. The aggregates consist of a rim of cells surrounding a hollow core. The cell line exhibits a unique pattern of mRNA expression with several molecules characteristic of the chondrocyte phenotype. Consistent with the chondrocyte phenotype, mRNAs encoding types IX and XI collagens were present along with an abundant expression of mRNAs encoding the core protein of the cartilage proteoglycans biglycan and aggrecan. No expression of mRNAs encoding types I or II fibrillar collagens or the proteoglycan decorin was observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of [35S]sulfate-radiolabeled material confirmed the translation of proteoglycans containing glycosaminoglycan chains. The expression of molecules that contribute to cartilage development and tumorigenesis was examined. The cell line produces abundant mRNA that encodes transforming growth factor-beta1, a member of a family of cartilage and bone inductive proteins. The expression of mRNA encoding two proteins associated specifically with chondrogenesis was detected: Cart-1, a homeobox protein involved in cartilage differentiation, and CD-RAP, a secreted molecule restricted under normal conditions to differentiating chondrocytes and cartilage. Overexpression of p53, a tumor-suppressor gene, was detected. DNA analysis revealed a loss of heterozygosity at the chromosomal locus encoding p53, with the deletion of one p53 allele and the mutation of the remaining allele in both the parent tumor and the cell line. The malignant chondrosarcoma phenotype may be related to the unique gene expression pattern that is characteristic in many ways of differentiating chondroblasts, as well as to the inactivation of the p53 function that could contribute to the proliferative capacity of the cell line. This cell line may serve as a biological model for further investigation of the etiology of human chondrosarcomas and for the synthesis and regulation of cartilage-specific genes.
U.S.-Mexican Relations: The 1980s and Beyond (1985)

That does the future hold for U.S.-Mexican relations? Optimistic assessments usually point to the high degree of interpenetration between the two societies, the recent history of intergovernmental cooperation, and the commonality of basic interests. Developments in one country have significant impact on the other, a process that now works both ways: the 1982 economic crisis in Mexico created serious difficulties for retailers on the U.S. side of the border, Mexico's subsequent cutbacks in imports prompted the loss of 200,000 jobs in the U.S., and Mexico's struggles with its international debt have crucial implications for banks in the U.S. Each country needs the other, and this kind of “interdependence” creates mutuality of purpose. According to this logic, the rational pursuit of national goals will build and fortify harmonious bilateral relations.
Mass spectrometry in combinatorial chemistry (2000)

In the fast expanding field of combinatorial chemistry, profiling libraries has always been a matter of concern--as illustrated by the buoyant literature over the past seven years. Spectroscopic methods, including especially mass spectrometry and to a lesser extent IR and NMR, have been applied at different levels of combinatorial library synthesis: in the rehearsal phase to optimize the chemistry prior to library generation, to confirm library composition, and to characterize after screening each structure that exhibits positive response. Most of the efforts have been concentrated on library composition assessment. The difficulties of such analyses have evolved from the infancy of the combinatorial concept, where large mixtures were prepared, to the recent parallel syntheses of collections of discrete compounds. Whereas the complexity of the analyses has diminished, an increased degree of automation was simultaneously required to achieve efficient library component identification and quantification. In this respect, mass spectrometry has been found to be the method of choice, providing rapid, sensitive, and informative analyses, especially when coupled to chromatographic separation. Fully automated workstations able to cope with several hundreds of compounds per day have been designed. After a brief introduction to describe the combinatorial approach, library characterization will be discussed in detail, considering first the solution-based methodologies and secondly the support-bound material analyses.
The Transmembrane Domains of Ectoapyrase (CD39) Affect Its Enzymatic Activity and Quaternary Structure (1998)

Mammalian ectoapyrase (CD39) is an integral membrane protein with two transmembrane domains and a large extracellular region. The enzymatic activity of ectoapyrase is inhibited by most detergents used for membrane protein solubilization. In contrast, the enzymatic activities of soluble E-type ATPases, including potato tuber (Solanum tuberosum) apyrase and parasite ecto-ATPase, are not affected by detergents. Here we show that ectoapyrase is a tetramer and that detergents that reduce the activity of the enzyme promote dissociation of the tetramer to monomers. We expressed a secreted form of the ectoapyrase in COS-7 cells by fusing the signal peptide of murine CD4 with the extracellular domain of the ectoapyrase. The soluble ectoapyrase is catalytically active and its activity is not affected by detergents. Mutants of the ectoapyrase with only the NH2- or the COOH-terminal transmembrane domain are membrane-bound, and their activity is no longer affected by detergents. The enzymatic activity of all of the mutant proteins is less than that of the native enzyme. These results suggest that the proper contacts between the transmembrane domains of the monomers in the tetramer are necessary for full enzymatic activity.
Highly Potent Geminal Bisphosphonates. From Pamidronate Disodium (Aredia) to Zoledronic Acid (Zometa) (2002)

Bisphosphonates (BPs) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED(50) of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.
Murine monoclonal anti-idiotype antibody as a potential network antigen for human carcinoembryonic antigen. (1990)

Carcinomas of the gastrointestinal tract are not curable by standard therapies. Thus, new therapeutic approaches for this disease are needed. This study proposes the use of anti-Id mAb as Ag substitutes to induce anti-tumor immunity in gastrointestinal cancer patients. Recently, we have generated and characterized one monoclonal anti-Id antibody, designated 3H1 (Ab2), which mimics biologically and antigenically a distinct and specific epitope of the 180,000 m.w. carcinoembryonic antigen (CEA) primarily expressed in high density by human pancreatic and colonic tumor cells. This epitope is unique to CEA and not present on other CEA-related lower m.w. members of the Ag family also found on normal tissues. The antigenic determinant as defined by the mAb 8019 (Ab1) against which the Ab2, 3H1 was raised, is absent on normal adult tissues by immunoperoxidase staining and haematopoietic cells including granulocytes by flow cytometry analysis. Anti-Id (Ab2) 3H1 induced CEA-specific antibodies in mice and rabbits. The immune sera from both mice and rabbits competed with Ab1 for binding to the colon carcinoma cell line LS174T and inhibited the binding of radioiodinated Ab1 to Ab2. This indicates that anti-anti-Id (Ab3) in mice and rabbits share idiotopes with Ab1 (8019). Furthermore, monoclonal Ab3 that bind to CEA have been generated from mice immunized with 3H1. The Ab3 (both polyclonal as well as monoclonal) immunoprecipitated the same 180,000 m.w. CEA as Ab1 (8019) by Western blotting analysis and showed almost identical immuno-staining patterns as Ab1 on colonic adenocarcinoma tissue sections from several patients. Collectively these data suggest that Ab2 3H1 could potentially be used clinically as a network Ag for immunotherapy of patients with CEA positive tumors.
Transcellular biosynthesis contributes to the production of leukotrienes during inflammatory responses in vivo (2002)

Leukotrienes are lipid mediators that evoke primarily proinflammatory responses by activating receptors present on virtually all cells. The production of leukotrienes is tightly regulated, and expression of 5-lipoxygenase, the enzyme required for the first step in leukotriene synthesis, is generally restricted to leukocytes. Arachidonic acid released from the cell membrane of activated leukocytes is rapidly converted to LTA(4) by 5-lipoxygenase. LTA(4) is further metabolized to either LTC(4) or LTB(4) by the enzyme LTC(4) synthase or LTA(4) hydrolase, respectively. Unlike 5-lipoxygenase, these enzymes are expressed in most tissues. This observation previously has led to the suggestion that LTA(4) produced by leukocytes may, in some cases, be delivered to other cell types before being converted into LTC(4) or LTB(4). While in vitro studies indicate that this process, termed transcellular biosynthesis, can lead to the production of leukotrienes, it has not been possible to determine the significance of this pathway in vivo. Using a series of bone marrow chimeras generated from 5-lipoxygenase- and LTA(4) hydrolase-deficient mice, we show here that transcellular biosynthesis contributes to the production of leukotrienes in vivo and that leukotrienes produced by this pathway are sufficient to contribute significantly to the physiological changes that characterize an ongoing inflammatory response.