gebhart/patrepeval huggingface dataset:
Basic fibroblast growth factor‐stimulated ex vivo expansion of haematopoietic progenitor cells from human placental and umbilical cord blood (2003)

We investigated whether basic fibroblast growth factor (bFGF) is effective in inducing ex vivo expansion of CD34+ haematopoietic progenitor cells derived from human placental and umbilical cord blood. bFGF significantly promoted the clonal growth of various haematopoietic progenitor cells, including granulocyte-macrophage colony-forming units (CFU-GM), mixed colony-forming units (CFU-Mix) and megakaryocyte colony-forming units (CFU-Meg) under semisolid culture conditions, with an optimal bFGF concentration of 30 ng/ml. CD34+ cells were then cultured in serum-free liquid medium containing various combinations of early-acting cytokines, including thrombopoietin (TPO), stem cell factor (SCF), interleukin 3 (IL-3) and flt3-ligand (FL), with or without bFGF, for 6 and 12 d. Without bFGF, TPO + IL-3, TPO + SCF + FL and TPO +SCF + IL-3 + FL dramatically increased the total numbers of erythroid progenitors, CFU-GM and CFU-Mix by d 12 of culture respectively. However, the addition of bFGF did not promote further proliferation of these progenitors, except for the erythroid progenitors, by d 6 when stimulated with all four cytokines. In contrast, total CFU-Meg numbers were approximately doubled when these cultures were supplemented with bFGF, producing 100- to 120-fold increases compared with the baseline control cultures. These results suggest that bFGF is effective in supporting the generation of megakaryocytic progenitor cells during ex vivo expansion.
Contrasting roles for all-trans retinoic acid in TGF-β–mediated induction of Foxp3 and Il10 genes in developing regulatory T cells (2009)

Extrathymic induction of regulatory T (T reg) cells is essential to the regulation of effector T cell responses in the periphery. In addition to Foxp3, T reg cell expression of suppressive cytokines, such as IL-10, is essential for peripheral tolerance, particularly in the intestines. TGF-beta has been shown to induce expression of Foxp3 as well as IL10 and the vitamin A metabolite; all-trans retinoic acid (RA [at-RA]) has been found to enhance the former. We report that in contrast to its enhancement of TGF-beta-mediated Foxp3 induction, at-RA potently inhibits the TGF-beta-mediated induction of Il10 in naive CD4 T cells. Thus, mucosal DC subsets that are active producers of at-RA inhibit induction of Il10 in naive CD4 T cells while promoting induction of Foxp3. Accordingly, mice with vitamin A deficiency have increased numbers of IL-10-competent T reg cells. Activation of DCs by certain Toll-like receptors (TLRs), particularly TLR9, suppresses T cell induction of Foxp3 and enables induction of Il10. Collectively, our data indicate that at-RA has reciprocal effects on the induction of Foxp3 and Il10 in developing CD4(+) T reg cells and suggest that TLR9-dependent inhibition of at-RA production by antigen-presenting cells might represent one mechanism to promote the development of IL-10-expressing T cells.
Synthesis and Energy-Transfer Properties of Hydrogen-Bonded Oligofluorenes (2005)

A set of fluorene oligomers has been synthesized by stepwise palladium-catalyzed (Suzuki) couplings of fluorene monomers. Ureidopyrimidinones (UPy), functional groups that can dimerize via quadruple hydrogen bonds, were attached to both ends of the oligofluorenes. The resulting bis-UPy-terminated oligomers self-assemble into supramolecular chain polymers. For comparison, oligofluorenes of the same oligomer lengths but without terminal hydrogen-bonding groups were synthesized. Chains of hydrogen-bonded fluorenes can be simply endcapped by a variety of chain stoppers, molecules that have one UPy group. In this manner, we have endcapped the hydrogen-bonded fluorene chains with either oligo(p-phenylenevinylene) or perylene bisimide. Energy-transfer experiments in solution and the solid state demonstrate that oligofluorenes can donate energy to a variety of energy acceptors, but that this energy transfer occurs most effectively when the donor fluorene is hydrogen-bonded to the acceptor.
Dipstick immunoassay to detect enterohemorrhagic Escherichia coli O157:H7 in retail ground beef (1992)

A sensitive and easy-to-perform dipstick immunoassay to detect Escherichia coli O157:H7 in retail ground beef was developed by using a sandwich-type assay (with a polyclonal antibody to E. coli O157 as the capture antibody and a monoclonal antibody to E. coli O157:H7 as the detection antibody) on a hydrophobic polyvinylidine difluoride-based membrane. E. coli O157:H7 in ground beef could be detected within 16 h, including incubation for 12 h in enrichment broth and the immunoassay, which takes 4 h. Pure culture cell suspensions of 10(5) or 10(6) E. coli O157:H7 organisms per ml produced intense color reactions in the immunoassay, whereas faint but detectable reactions occurred with 10(3) CFU/ml. The sensitivity of the combined enrichment-immunoassay procedure as determined by using ground beef inoculated with E. coli O157:H7 was 0.1 to 1.3 cells per g, with a false-positive rate of 2.0%. A survey of retail ground beef using this procedure revealed that 1 of 76 samples was contaminated by E. coli O157:H7.
PLC-β3 signals upstream of PKCε in acute and chronic inflammatory hyperalgesia (2007)

While protein kinase C epsilon has been shown to contribute to acute and chronic mechanical hyperalgesia, its upstream signaling pathway has received little attention. Since phospholipase C can signal to PKC epsilon and has been implicated in nociceptor sensitization, we tested if it is upstream of PKC epsilon in mechanisms underlying primary mechanical hyperalgesia. In the rat, the PKC epsilon-dependent mechanical hyperalgesia and hyperalgesic priming (i.e., a form of chronic latent enhanced hyperalgesia) induced by carrageenan were attenuated by a non-selective PLC inhibitor U-73122. A lipid mediator of PLC signaling, l-alpha-lysophosphatidylcholine produced dose-dependent mechanical hyperalgesia and hyperalgesic priming, which was attenuated by EAVSLKPT, a selective PKC epsilon inhibitor. However, U-73122 did not attenuate hyperalgesia induced by psi epsilon RACK, a selective PKC epsilon activator. Antisense to PLC-beta 3 isoform, which was found in small-diameter dorsal root ganglion neurons, also attenuated carrageenan-induced acute and chronic-latent hyperalgesia. These studies support the suggestion that PLC-beta 3 is an important upstream signaling molecule for PKC epsilon-mediated acute and chronic inflammatory pain.
Signalling through cyclic nucleotide monophosphates in cyanobacteria (2003)

Summary The cyanobacteria are a diverse group of photosynthetic prokaryotes, of which many species synthesize cyclic nucleotide monophosphates. The role of cyclic nucleotide monophosphates in cyanobacterial biology has been studied through phenotypic, molecular, genetic, and computer‐based analyses and here I review the history of the field. The study of cyclic nucleotide monophosphates in cyanobacteria has been informed by experiments performed in unrelated organisms but recent investigations have, however, demonstrated that scientific principles, applicable to a wide range of species, can be derived from the study of cyclic nucleotide biology in cyanobacteria and I detail some of this work. Contents Summary 23 I. Introduction 23 II. Cyclic nucleotide monophosphates 24 III. cNMPs and their roles in cyanobacteria 26 IV. Molecular identification of components of the cNMP signalling pathway in cyanobacteria 27 V. Lessons from cAMP signalling in cyanobacteria for other organisms 30 Acknowledgements 31 References 32
1H NMR Studies of Interleukin 8 Analogs: Characterization of the Domains Essential for Function (1994)

1H NMR studies were carried out on interleukin 8 (IL-8) analogs in order to probe the structural features that are essential for receptor binding and function. The analogs studied were the chemically synthesized IL-8 (1-72), a series of N-terminally truncated derivatives (4-72, 5-72, and 6-72), and derivatives with single amino acid substitutions (I10A, R6K, and H33A). Previous functional studies have shown that the N-terminal residues, especially the residues at positions 4-6, and the beta turn containing Cys-34, which is disulfide linked to Cys-7, are important for receptor affinity and functional activity [Clark-Lewis, I., Schumacher, C., Baggiolini, M., & Moser, B. (1991) J. Biol. Chem. 266, 23128-23134; Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., & Baggiolini, M. (1994) J. Biol. Chem. (in press)]. The 6-72 and R6K analogs also showed properties of an antagonist. Analysis of the 1H NMR parameters such as chemical shifts, amide proton chemical shift temperature coefficients, and NOESY data indicates that the core structure is the same for all these proteins. Small differences were observed in some of the NMR properties for some of the residues in the N-terminal region and the turn containing Cys-34. Detailed analysis suggests that there is no correlation between these differences and observed function. Thus functional differences between the N-terminal analogs are a direct consequence of changes in receptor binding due to substitutions/deletions in the N-terminal sequence and not due to structural changes elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of the inhibition of reverse transcription by antisense oligonucleotides. (1992)

We have demonstrated that the synthesis of cDNA by avian myeloblastosis virus and Moloney murine leukemia virus reverse transcriptases can be prevented by oligonucleotides bound to the RNA template approximately 100 nucleotides remote from the 3' end of the primer. The RNA was truncated at the level of the antisense oligonucleotide-RNA duplex during the reverse transcription. The key role played by the reverse transcriptase-associated RNase H activity in the inhibition process was shown by the use of (i) inhibitors of RNase H (NaF or dAMP), (ii) Moloney murine leukemia virus reverse transcriptase devoid of RNase H activity, or (iii) alpha-analogues of oligomers that do not elicit RNase H-catalyzed RNA degradation. In all three cases the inhibitory effect was either reduced (NaF, dAMP) or totally abolished. However, an alpha-oligomer bound to the sequence immediately adjacent to the primer-binding site prevented reverse transcription. Therefore, initiation of polymerization can be blocked by means of an RNase H-independent mechanism, whereas arrest of a growing cDNA strand can be achieved only by an oligonucleotide mediating cleavage of the template RNA.
Nonfouling Behavior of Polycarboxybetaine-Grafted Surfaces: Structural and Environmental Effects (2008)

Zwitterionic carboxybetaine (CB) has unique dual functionality for ligand immobilization on a nonfouling background. The properties of CB groups depend on their spacer groups between the positive quaternary amine groups and the negative carboxyl groups and environmental factors (e.g., ionic strengths and pH values). In this work, five polycarboxybetaines were prepared, including one polycarboxybetaine methacrylate (polyCBMA) and four polycarboxybetaine acrylamides (polyCBAAs) with different spacer groups. The polymers were grafted from a gold surface covered with initiators using surface-initiated atom transfer radical polymerization. Fibrinogen adsorption was measured as a function of ionic strengths and pH values using surface plasmon resonance sensors. The responsive protein adsorption on four polyCBAAs was mapped out. Results show that most of these surfaces exhibit high protein resistance in a wide range of ionic strengths and are more effective than zwitterionic self-assembled monolayers. Although protein adsorption tends to increase at low ionic strength and low pH value, it is still very low for polycarboxybetaines with a methylene, an ethylene, or a propylene spacer group but is more evident for polyCBAA with a longer spacer group (i.e., a pentene group). The response to ionic strengths and pH values can be attributed to the antipolyelectrolyte and protonation/deprotonation properties of polycarboxybetaines, respectively. Both of these properties are related to the spacer groups of CBs.
Integrated single and two-phase micro heat sinks under IGBT chips (1999)

Experiments have been performed to assess the feasibility of single and two-phase micro heat exchangers applied to the cooling of insulated gate bipolar transistor (IGBT) power components. After a brief recall of the principal characteristics of such heat exchangers, prototypes that have been built and tested are described. Then, the experimental measurements are compared to the predictions of the thermal and hydraulic performance with water and the inert fluorocarbon liquid (FC72) as coolant fluids.
Effects of a potent synthetic melanotropin, Nle4-D-Phe7-α-MSH (Melanotan-I) on tanning: a dose-ranging study (1999)

An open-label, dose-finding study of a superpotent melanotropic peptide [Nle4-D-Phe7]α-MSH1-13, called Melanotan-I (MT-I), was performed in eight male volunteers with “tannable” skin types III-IV. This synthetic analog of α-melanocyte-stimulating hormone (α-MSH), was administered subcutaneously for 10 days at three dose levels of 0.16 mg/kg per dose, 0.26 mg/kg per dose and 0.4 mg/kg per dose. Skin pigmentation at eight anatomic sites was measured serially using light reflectance values quantitated as luminance (L-values) and blue-yellow hue (b-values). All subjects tanned during the course of the trial, but there was no evidence of improved tanning beyond that obtained at the 0.16 mg/kg dose (P = 0.04). The most responsive site of skin darkening was the forehead, followed by the cheek, chin, neck and forearm. The anterior leg and buttock did not darken. There were no toxicities of grade 2 or more by World Health Organization (WHO) criteria at the 0.16 mg/kg dose, whereas the two higher doses produced moderate gastrointestinal upset and some mild to moderate fatigue. The optimal dose for ten daily subcutaneous injections of this agent is 0.16 mg/kg per day.
Broad host range plasmids carrying theEscherichia colilactose and galactose operons (1992)

We have developed a number of broad-host-range plasmids that allow the expression of the Escherichia coli lac operon from any cloned promoter, and the creation of ‘in phase’ fusions between lacZ and other cloned genes. In a second series of constructions, the E. coli gal operon has been cloned into the broad-host-range vector and a plasmid carrying both the E. coli gal and lac genes is described. These plasmids have been transferred into Pseudomonas aeruginosa and Zymomonas mobilis and their effects on the utilisation of lactose and galactose have been investigated.
Identification of Periodontal Pathogens in Atheromatous Plaques (2000)

Periodontal pathogens are present in atherosclerotic plaques where, like other infectious microorganisms such as C. pneumoniae, they may play a role in the development and progression of atherosclerosis leading to coronary vascular disease and other clinical sequelae.
Stable Docking of Neutralizing Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Monoclonal Antibodies 2F5 and 4E10 Is Dependent on the Membrane Immersion Depth of Their Epitope Regions (2009)

The binding of neutralizing antibodies 2F5 and 4E10 to human immunodeficiency virus type 1 (HIV-1) gp41 involves both the viral membrane and gp41 membrane proximal external region (MPER) epitopes. In this study, we have used several biophysical tools to examine the secondary structure, orientation, and depth of immersion of gp41 MPER peptides in liposomes and to determine how the orientation of the MPER with lipids affects the binding kinetics of monoclonal antibodies (MAbs) 2F5 and 4E10. The binding of 2F5 and 4E10 both to their respective nominal epitopes and to a biepitope (includes 2F5 and 4E10 epitopes) MPER peptide-liposome conjugate was best described by a two-step encounter-docking model. Analysis of the binding kinetics and the effect of temperature on the binding stability of 2F5 and 4E10 to MPER peptide-liposome conjugates revealed that the docking of 4E10 was relatively slower and thermodynamically less favorable. The results of fluorescence-quenching and fluorescence resonance energy transfer experiments showed that the 2F5 epitope was more solvent exposed, whereas the 4E10 epitope was immersed in the polar-apolar interfacial region of the lipid bilayer. A circular dichroism spectroscopic study demonstrated that the nominal epitope and biepitope MPER peptides adopted ordered structures with differing helical contents when anchored to liposomes. Furthermore, anchoring of MPER peptides to the membrane via a hydrophobic anchor sequence was required for efficient MAb docking. These results support the model that the ability of 2F5 and 4E10 to bind to membrane lipid is required for stable docking to membrane-embedded MPER residues. These data have important implications for the design and use of peptide-liposome conjugates as immunogens for the induction of MPER-neutralizing antibodies.
Facile preparation of carbon-supported Pd nanoparticles for electrocatalytic oxidation of formic acid (2008)

A low-temperature approach via the complexing of PdCl 2 with EDTA followed by NaBH 4 reduction has been used to prepare Vulcan XC-72 carbon-supported Pd nanoparticles (Pd/C). The mean particle size of the Pd/C catalysts is found to increase from 3.3 to 9.2 nm with heat-treated temperature. TEM images demonstrated that the Pd nanoparticles are well dispersed on the support, with a relatively narrow particle size distribution. A correlation between the electrocatalytic activity of formic acid oxidation and the particle size of the Pd/C catalysts indicates that the highest activity of formic acid oxidation is found with a Pd mean particle size of ca. 4.7 nm. The preparation method used here is cost-effective and should be easily scaled for industrial production.
Quantum Size Effect in Three-Dimensional Microscopic Semiconductor Crystals (2023)

The exciton absorption spectrum of microscopic CuCl crystals grown in a transparent dielectric matrix has been studied. The size of the microscopic crystals was varied in a controlled manner from several tens of angstroms to hundreds of angstroms. There is a short-wave shift (of up to 0.1 eV) of the exciton absorption lines, caused by a quantum size effect.
ChemInform Abstract: A Novel Dicyanotriterpenoid, 2‐Cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐onitrile, Active at Picomolar Concentrations for Inhibition of Nitric Oxide Production (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson’s disease (2007)

Progressive loss of dopaminergic neurons in the substantia nigra pars compacta and their terminal connections in the striatum are central features in Parkinson's disease (PD). Emerging evidence supports the notion that microglia neuroinflammatory responses speed neurodegenerative events. We demonstrated previously that this can be slowed by adoptive transfer of T cells from Copolymer-1-immunized mice administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) recipients. The cellular basis for this neuroprotective response was the CD4+ T cell population, suggesting involvement of CD4+CD25+ regulatory T cells (Tregs), cells known to suppress immune activation and maintain immune homeostasis and tolerance. We show for the first time that adoptive transfer of CD3-activated Tregs to MPTP-intoxicated mice provides greater than 90% protection of the nigrostriatal system. The response was dose-dependent and paralleled modulation of microglial responses and up-regulation of glial cell-derived neurotrophic factor (CDNF) and TGF-beta. Interestingly, that adoptive transfer of effector T cells showed no significant neuroprotective activities. Tregs were found to mediate neuroprotection through suppression of microglial responses to stimuli, including aggregated, nitrated alpha-synuclein. Moreover, Treg-mediated suppression was also operative following removal of Tregs from culture prior to stimulation. This neuroprotection was achieved through modulation of microglial oxidative stress and inflammation. As Tregs can be modulated in vivo, these data strongly support the use of such immunomodulatory strategies to treat PD.
Transfection of NK Cells with mRNA or Lentivirus Expressing Chimeric Antigen Receptors Results in Highly Efficient Killing of Lymphoid Malignancies and Compares Favorably with Monoclonal Antibody-Directed ADCC. (2009)

Abstract Abstract 1696 Poster Board I-722 NK cells frequently do not kill malignant lymphoid target cells except through antibody dependent cellular cytotoxicity (ADCC) when combined with monoclonal antibodies (mAb). Here we compared the ability of the human NK cell line NK-92 to lyse lymphoid cell lines and primary chronic lymphoid leukemia (CLL) cells after transfection with either mRNA or lentivirus coding for Chimeric Antigen Receptors (CAR) against CD19 or CD20. Electroporation (Genepulser, Biorad) of 10 μg mRNA (coding for GFP, CD19-CAR or CD20-CAR) into NK-92 cells was performed at 300V and 150 μF (Leuk. Res 2009;33:1255). For lentivirus transduction, CD19-CAR and CD20-CAR were cloned into a pCL20c IRES-GFP vector and lentivirus stocks for GFP, CD19-CAR and CD20-CAR were obtained from 293T packaging cells. NK-92 cells were transduced by two successive rounds of spinfection in the presence of 8 μg/ml protamine sulfate. Mean transfection efficiencies were 57.2% ± 6.6 for electroporation with mRNA, and 32.6% ± 4.1 for lentivirus transduction. The cytotoxity of the transfected/transduced NK-92 cells against the reference Raji cell line was not affected. The NK-92 resistant cell lines SUP-B15 (CD19+/CD20-) and TMD5 (CD19+/CD20+) became highly sensitive to lysis by transfected NK-92 expressing CD19-CAR, while only TMD5 became sensitive to transfected NK-92 expressing CD20-CAR. Importantly, mRNA-transfected NK-92 showed two-fold higher killing compared to lentivirus-transduced NK-92 despite similar receptor expression. As expected, expression of CAR following mRNA transfection was temporary (48 hours), whereas lentivirus transduced NK-92 maintained CAR expression and cytolytic function for indefinite periods in culture. In order to obtain higher target cell killing by lentivirus transduced cells, NK-92 cells could be highly enriched by cell sorting. Subsequently, we compared CAR-directed killing with ADCC on primary B-CLL patient samples, using NK-92 cells genetically modified by lentivirus expressing anti-CD20 CAR versus high affinity Fc receptor-expressing (FcRγIIIA) NK-92 cells combined with the anti-CD20 monoclonal antibody Rituximab. Initially all CLL cells were resistant to killing by NK-92. Anti-CD20 CAR transfected NK-92 cells showed significantly higher cytotoxicity than ADCC against patients' cells, with less patient-to-patient variability. In conclusions, transfection of NK cells with mRNA coding for CAR against lymphoid surface antigens is a highly efficient method that can easily be scaled up to produce clinical grade material. Lentivirus transduced NK-92 cells show stable expression of CAR, but efficient killing requires sorting or selection for transfected cells. CAR-directed killing by NK-92 compares favorably with anti-CD20 mAb mediated ADCC against primary CLL targets and either approach, alone or in combination, could have clinical relevance. Disclosures Klingemann: ZelleRx Corp.: Co-founder and shareholder.