gebhart/patrepeval huggingface dataset:
The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination (1987)

The process by which leukemogenic viruses are generated during the lifetime of certain strains of mice is poorly understood. We have therefore set out to define all the murine leukemia virus-related endogenous proviruses of HRS/J mice. We have cloned 34 different proviral fragments and their flanking cellular sequences. These have been characterized by restriction enzyme analysis, by fingerprinting in vitro-synthesized RNA, and by DNA sequencing. We conclude that all the proviruses can be assigned into one of four different classes: the previously characterized ecotropic, xenotropic, and polytropic viruses, as well as a new class we have termed modified polytropic viruses. The xenotropic, polytropic, and modified polytropic classes are closely related to one another, but as a group they differ considerably from the ecotropic class. Sequence analyses show that both polytropic and modified polytropic sequences can contribute env sequences to recombinant viruses.
Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines (2017)

We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs. IL-2R-expressing cells, (b) avoiding any FcγR-binding and Fc effector functions and (c) reduced binding to endothelial cells expressing CD25; and (iii) improve the pharmacokinetics, and thus convenience of administration, of IL-2. The crystal structure of the IL2v-IL-2Rβγ complex was determined and CEA-IL2v activity was assessed using human immune effector cells. Tumor targeting was investigated in tumor-bearing mice using <sup>89</sup>Zr-labeled CEA-IL2v. Efficacy studies were performed in (a) syngeneic mouse models as monotherapy and combined with anti-PD-L1, and in (b) xenograft mouse models in combination with ADCC-mediating antibodies. CEA-IL2v binds to CEA with pM avidity but not to CD25, and consequently did not preferentially activate Tregs. <i>In vivo</i>, CEA-IL2v demonstrated superior pharmacokinetics and tumor targeting compared with a wild-type IL-2-based CEA immunocytokine (CEA-IL2wt). CEA-IL2v strongly expanded NK and CD8<sup>+</sup> T cells, skewing the CD8<sup>+</sup>:CD4<sup>+</sup> ratio toward CD8<sup>+</sup> T cells both in the periphery and in the tumor, and mediated single agent efficacy in syngeneic MC38-CEA and PancO2-CEA models. Combination with trastuzumab, cetuximab and imgatuzumab, all of human IgG1 isotype, resulted in superior efficacy compared with the monotherapies alone. Combined with anti-PD-L1, CEA-IL2v mediated superior efficacy over the respective monotherapies, and over the combination with an untargeted control immunocytokine. These preclinical data support the ongoing clinical investigation of the cergutuzumab amunaleukin immunocytokine with abolished CD25 binding for the treatment of CEA-positive solid tumors in combination with PD-L1 checkpoint blockade and ADCC competent antibodies.
Of men in mice: the success and promise of humanized mouse models for human malaria parasite infections (2014)

Forty percent of people worldwide are at risk of malaria infection, and despite control efforts it remains the most deadly parasitic disease. Unfortunately, rapid discovery and development of new interventions for malaria are hindered by the lack of small animal models that support the complex life cycles of the main parasite species infecting humans. Such tools must accommodate human parasite tropism for human tissue. Mouse models with human tissue developed to date have already enhanced our knowledge of human parasites, and are useful tools for assessing anti-parasitic interventions. Although these systems are imperfect, their continued refinement will likely broaden their utility. Some of the malaria parasite's interactions with human hepatocytes and human erythrocytes can already be modelled with available humanized mouse systems. However, interactions with other relevant human tissues such as the skin and immune system, as well as most transitions between life cycle stages in vivo will require refinement of existing humanized mouse models. Here, we review the recent successes achieved in modelling human malaria parasite biology in humanized mice, and discuss how these models have potential to become a valuable part of the toolbox used for understanding the biology of, and development of interventions to, malaria.
Monitoring of Reaction Intermediates in the Gas Phase: Ruthenium-Catalyzed C–C Coupling (2014)

Investigation of catalytic organometallic reactions often relies on mass spectrometry. Frequently, however, possible reaction intermediates along the catalytic cycle correspond to the same mass-to-charge ratio and have rather similar molecular composition. We have shown for the C–C coupling between phenylacetylene and pyridine catalyzed by the ruthenium complex [RuCp(PPh3)(Py)2]+ that using a combination of collision-induced dissociation experiments, infrared multiphoton dissociation spectroscopy, bimolecular reactions, and DFT calculations it is possible to study isobaric complexes and characterize the key intermediates in the reaction cycle. In addition, a so far elusive ruthenium complex with π-coordinated alkyne molecule has been spectroscopically characterized.
Infectious bursal disease (Gumboro disease). (2000)

Infectious bursal disease (IBD) (Gumboro disease) has been described throughout the world, and the socio-economic significance of the disease is considerable world-wide. Various forms of the disease have been described, but typing remains unclear, since antigenic and pathotypic criteria are used indiscriminately, and the true incidence of different types is difficult to determine. Moreover, the infection, when not fatal, leads to a degree of immunosuppression which is often difficult to measure. Finally, the control measures used are subject to variations, and seldom follow a specific or standardised plan. In the context of expanding international trade, the authors provide an overview of existing knowledge on the subject to enhance available information on the epidemiology of IBD, the identification of reliable viral markers for diagnosis, and the implementation of specific control measures to ensure a global and co-ordinated approach to the disease.
The cyclic expression of CD45R isoforms on CD4 T cells (1992)

Conference Article| February 01 1992 The cyclic expression of CD45R isoforms on CD4 T cells Eric B. Bell; Eric B. Bell 1Immunology Research Group, Cell and Structural Biology, Medical School, University of Manchester, Manchester M13 9PT, U.K. Search for other works by this author on: This Site PubMed Google Scholar Chun-ping Yang; Chun-ping Yang 1Immunology Research Group, Cell and Structural Biology, Medical School, University of Manchester, Manchester M13 9PT, U.K. Search for other works by this author on: This Site PubMed Google Scholar Sally R. Sarawar; Sally R. Sarawar 1Immunology Research Group, Cell and Structural Biology, Medical School, University of Manchester, Manchester M13 9PT, U.K. Search for other works by this author on: This Site PubMed Google Scholar Sheila M. Sparshott Sheila M. Sparshott 1Immunology Research Group, Cell and Structural Biology, Medical School, University of Manchester, Manchester M13 9PT, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1992) 20 (1): 198–202. https://doi.org/10.1042/bst0200198 Article history Received: September 09 1991 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Eric B. Bell, Chun-ping Yang, Sally R. Sarawar, Sheila M. Sparshott; The cyclic expression of CD45R isoforms on CD4 T cells. Biochem Soc Trans 1 February 1992; 20 (1): 198–202. doi: https://doi.org/10.1042/bst0200198 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: IL-2, interleukin 2, GVH, graft versus host, TDL, thoracic-duct lymphocytes, PBL, peripheral-blood lymphocytes, SP, single positive, RTE, recent thymic emigrants This content is only available as a PDF. © 1992 Biochemical Society1992 Article PDF first page preview Close Modal You do not currently have access to this content.
Control of Larval Development by Chemosensory Neurons in Caenorhabditis elegans (1991)

Larval development of the nematode Caenorhabditis elegans is controlled by the activities of four classes of chemosensory neurons. The choice between normal development and development into a specialized larval form called a dauer larva is regulated by competing environmental stimuli: food and a dauer pheromone. When the neuron classes ADF, ASG, ASI, and ASJ are killed, animals develop as dauer larvae regardless of environmental conditions. These neurons might sense food or dauer pheromone, or both, to initiate the specialized differentiation of many cell types that occurs during dauer formation. Entry into and exit from the dauer stage are primarily controlled by different chemosensory neurons. The analysis of mutants defective in dauer formation indicates that the chemosensory neurons are active in the absence of sensory inputs and that dauer pheromone inhibits the ability of these neurons to generate a signal necessary for normal development.
Intrathecal inflammation precedes development of Alzheimer's disease (2003)

These results demonstrate increased production of the proinflammatory cytokine, TNFalpha and decreased production of the anti-inflammatory cytokine TGFbeta in patients with MCI at risk to develop AD, suggesting a propensity towards inflammation in this patient group and indicating that CNS inflammation is a early hallmark in the pathogenesis of AD.
Elevated Cyclic AMP Inhibits NF-κB-mediated Transcription in Human Monocytic Cells and Endothelial Cells (1996)

The NF-kappaB/Rel family of transcription factors regulates the inducible expression of many genes in activated human monocytes and endothelial cells. In this study, we examined the molecular mechanism by which agents that elevate intracellular cAMP inhibit the expression of the tumor necrosis factor alpha (TNFalpha), tissue factor, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1 genes. Both forskolin and dibutyryl cAMP, which elevate intracellular cAMP by independent mechanisms, inhibited TNFalpha and tissue factor expression at the level of transcription. Induction of NF-kappaB-dependent gene expression in transiently transfected human monocytic THP-1 cells and human umbilical vein endothelial cells was inhibited by elevated cAMP and by overexpression of the catalytic subunit of protein kinase A (PKA). Elevated cAMP did not prevent nuclear translocation of p50/p65 and c-Rel/p65 heterodimers, decrease nuclear translocation of p65, or significantly modify TNFalpha-induced phosphorylation of p65. Functional studies demonstrated that transcriptional activation of a plasmid containing multimerized kappaB sites by p65 was inhibited by agents that elevate cAMP and by overexpression of the catalytic subunit of PKA. This study indicates that activation of PKA reduces the induction of a distinct set of genes in monocytes and endothelial cells by inhibiting NF-kappaB-mediated transcription.
Length Separation of Zwitterion-Functionalized Single Wall Carbon Nanotubes by GPC (2002)

The length-fractionation of shortened (250 to 25 nm), zwitterion-functionalized, single wall carbon nanotubes (SWNTs) has been demonstrated via gel permeation chromatography (GPC). The UV-Vis spectrum of each fraction indicates an apparent "solubilization", as evident by the direct observation of all predicted optically allowed interband transitions between the mirror image spikes in the density of states of both metallic and semiconducting SWNTs with various tube diameters. As evident by the presence or absence of the 270 nm, pi-plasmon absorption, this "solubilization" is a dynamic process and leads to re-aggregation if left undisturbed for a couple of weeks or upon dissociation of the pendant octadecylamine groups. This non-destructive and highly versatile separation methodology opens up an array of possible applications for shortened SWNTs in nanostructured devices.
Factors modifying protective effect of anti-CD18 antibodies on myocardial reperfusion injury in dogs (1996)

Anti-CD18 monoclonal antibodies (MAb) have demonstrated variable protection against neutrophil (PMN)-mediated myocardial reperfusion injury. To identify factors contributing to this variability, open-chest dogs underwent coronary artery occlusion for 90 min followed by reperfusion for 3.5 h. Ten minutes before reperfusion the dogs received saline (n = 18) or one of three anti-CD18 MAb: MHM.23, R15.7, or PLM-2 (2, 1, and 1 mg/kg and n = 19, 8, and 4, respectively). Collateral flow was measured with radioactive microspheres, area at risk was assessed with monastral blue dye, and infarct size was measured postmortem by triphenyltetrazolium chloride. In vitro, all three MAb bound to canine PMNs, but only MHM.23 and R15.7 inhibited their adherence to keyhole limpet hemocyanin-coated plastic. In vivo, only MHM.23 and R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow. MHM.23 afforded protection in dogs with moderate ischemia (epicardial collateral flow > 0.1 ml.min-1.g-1, infarct size reduced 46%) but not in dogs with more severe ischemia. Only R15.7 was effective in dogs with severe ischemia. Although MHM.23 and R15.7 produced similar inhibition of tissue PMN accumulation, as reflected by myeloperoxidase activity. R15.7 markedly inhibited H2O2 production by PMNs after exposure to platelet-activating factor, whereas MHM.23 had only a minimal effect. The effectiveness of different anti-CD18 MAb in preventing reperfusion injury appears to be 1) highly dependent on the specific anti-CD18 MAb employed, 2) predicted only partially by in vitro binding to PMNs, static in vitro tests of PMN adherence, or the extent of inhibition of PMN accumulation in vivo, 3) related more to their ability to inhibit oxidant release from activated PMNs, and 4) strongly influenced by the severity of myocardial ischemia before reperfusion.
Structural Basis of the Intrasteric Regulation of Myosin Light Chain Kinases (1992)

The smooth muscle myosin light chain kinase (smMLCK) catalytic core was modeled by using the crystallographic coordinates of the cyclic AMP-dependent protein kinase catalytic subunit (cAPK) and a bound pseudosubstrate inhibitor peptide, PKI(5-24). Despite only 30% identity in amino acid sequence, the MLCK sequence can be readily accommodated in this structure. With the exception of the short B-helix, all major elements of secondary structure in the core are very likely conserved. The active site of the modeled MLCK complements the known requirements for peptide substrate recognition. MLCK contains a pseudosubstrate sequence that overlaps the calmodulin binding domain and has been proposed to act as an intrasteric inhibitor and occupy the substrate binding site in the absence of Ca(2+)-calmodulin. The pseudosubstrate sequence can be modeled easily into the entire backbone of PKI(5-24). The results demonstrate that the intrasteric model for regulation of MLCK by intramolecular competitive inhibition is structurally plausible.
Enhancement of Monoclonal Antibody Efficacy: The Effect of External Beam Radiation (1995)

External beam irradiation has been shown to enhance accumulation of monoclonal antibodies (MAb) in tumors in vivo. This effect is mainly attributed to an unspecific damage of vascular endothelial cells resulting in an increased vascular leakage. The aim of our studies was to determine the effects of external beam radiation on the expression and function of the epidermal growth factor receptor (EGF-R) in vivo. Expression and internalization of EGF-R was tested in vivo, employing 125I-MAb 425 that binds specifically to the human EGF-R. Irradiation of human high-grade glioma cell lines U87-MG and A1207 with increasing doses (0-3600 Rad) of 240 kVp X-rays, markedly enhanced the binding of 125I-MAb 425 to the cell surface. This effect could only be observed for a few days following irradiation. No correlation of the radiation dose and overexpression of EGF-R were found. At the same time, irradiation stimulated significant and dose-dependent internalization of 125I-MAb. Internalization and intranuclear accumulation of 125I-MAb are necessary to explain the radiocytotoxic effects of 125I. The combination of external beam irradiation and labeled MAb 425 showed at least additive effects on tumor cell survival, when the interval between irradiation and MAb treatment was short. Our data support the clinical observations in the adjuvant treatment of high grade gliomas with 125I-MAb 425 following surgery and external beam radiation.
Lentiviral vectors: optimization of packaging, transduction and gene expression (2004)

Gene transfer vectors based on retroviruses including oncogenic retroviruses and lentiviruses provide effective means for the delivery, integration and expression of exogenous genes in mammalian cells. Lentiviral (LV) vectors provide attractive gene delivery vehicles in the context of non-dividing cells. This review summarizes the different optimized LV genetic systems that have been developed to date. In all cases, the production of LV-derived vectors consists of a genetically split gene expression design. The viral elements that are specifically required are (i). the LV packaging helper proteins consisting of at least the gag-pol genes, (ii). the LV transfer vector RNA containing the transgene expression cassette, and (iii). an heterologous glycoprotein. While the genetic requirements and performances of the two former viral elements will be treated herein, the latter element relative to the envelope pseudotyping of LV vectors will not be further described (cf. review by Cosset in this issue).
Ambient Aerodynamic Desorption/Ionization Method for Microparticle Mass Measurement (2013)

An ambient desorption/ionization method, named aerodynamic desorption (AD), was proposed for the in situ rapid mass measurement of microparticles. The AD method exploited the discontinuous atmospheric pressure interface (DAPI) to generate a pulsed airflow, which was used to desorb the microparticles under atmospheric pressure. Various microparticles, e.g., bacteria, cell, polystyrene, synthetic diamond, and silica particles, with different size and surface component were successfully desorbed. Similar to that in the conventional laser-induced acoustic desorption (LIAD) method, these microparticles were desorbed as precharged ions in the AD process and the charge number was largely relevant to the particle size. However, compared with LIAD, the sensitivity of the AD method was higher. A lower concentration of particles was required for the analysis. In addition, the construction and sampling process of AD source were much simpler. All types of liquid, solid, or/and gaseous samples can be directly sampled under ambient condition. As a demonstration of this AD method, the in situ mass analysis of red blood cells (RBCs) and E. coli bacteria were carried out using a homemade ambient AD mass spectrometer consisting of AD source, QIT mass analyzer, and charge detector. Their mass and mass distributions were obtained successfully.
T (Thomsen-Friedenreich) and Tn epitope location and their spatial relations to adhesion plaques on human breast carcinoma cells: immunogold-silver staining studies at scanning electron microscopic level. (1998)

T and Tn are pancarcinoma epitopes (EPs) which can be immunodetected in about 90% of adenocarcinomas (CAs). To study the location of T and Tn EPs and their relations to adhesion plaques on CA cells, immunogold-silver staining method was employed at scanning electron microscope (SEM) level. Human breast CA cells grown on coverslips were fixed in paraformaldehyde and glutaraldehyde, reacted with cocktails of monoclonal antibodies against T or Tn EPs, followed by incubation with 10 nm gold conjugated goat anti-mouse immuno-globulins. The positive gold particle labelling was amplified with silver enhancement solution, and the specimens were then routinely critical point dried, sputter-coated with palladium and observed under SEM. The studies show that T and Tn EPs are not randomly distributed on CA cell surface; they are aggregated at the adhesion plaque area. These results confirm that T and Tn EPs play roles in CA cell adhesion, and suggest that they may represent the initial points of contact by immuno-effectors and therefore can be utilized in immunointervention and anti-adhesion therapy against CA.
Phylogenetic Relationships of Xylella fastidiosa Strains Isolated from Landscape Ornamentals in Southern California (2007)

ABSTRACT Xylella fastidiosa is an insect-borne, xylem-limited pathogenic bacterium that has been associated with a rise in incidence of diseased landscape ornamentals in southern California. The objective of this study was to genetically characterize strains isolated from ornamental hosts to understand their distribution and identity. Strains of X. fastidiosa isolated from ornamentals were characterized using a multiprimer polymerase chain reaction (PCR) system, random amplified polymorphic DNA (RAPD)-PCR, and sequence analysis of the 16S-23S rDNA intergenic spacer region (ISR). Based on RAPD-PCR and 16S-23S rDNA ISR, strains isolated from daylily, jacaranda, and magnolia clustered with members of X. fastidiosa subsp. sandyi and caused oleander leaf scorch but not Pierce's disease symptoms in glasshouse assays on oleander and grape, respectively. This demonstrated both that our groupings based on genetic characterization were valid and that strains of X. fastidiosa subsp. sandyi are present in hosts other than oleander. Strains isolated from Spanish broom, cherry, and one strain isolated from western redbud clustered with X. fastidiosa subsp. fastidiosa members. Strains isolated from purple-leafed plum, olive, peach, plum, sweetgum, maidenhair tree, crape myrtle, and another western redbud strain clustered with members of X. fastidiosa subsp. multiplex. All strains isolated from mulberry and one from heavenly bamboo formed a separate cluster that has not yet been defined as a subspecies.