gebhart/patrepeval huggingface dataset:
Pharmacokinetics and Biological Activity of Atacicept in Patients With Rheumatoid Arthritis (2008)

Atacicept is a recombinant fusion protein containing the extracellular ligand-binding portion of the transmembrane activator and CAML interactor (TACI, CD267) receptor and inhibits B lymphocyte stimulator (BLyS, CD257) and a proliferation-inducing ligand (APRIL, CD256), both potent stimulators of B cell maturation, proliferation, and survival. Atacicept pharmacokinetics and pharmacodynamics were assessed in a double-blind, placebo-controlled, phase I study in patients with active, moderate to severe rheumatoid arthritis receiving atacicept either as a single subcutaneous or repeated, every other week dose. Pharmacokinetic profiles were determined by measuring serum concentrations of free atacicept and its complex with BLyS. Nonspecific immunoglobulin (Ig)M, IgG, and IgA; IgM-RF (rheumatoid factor), IgG-RF, and IgA-RF antibody levels; and B cell profiles provided markers of biological activity. Pharmacokinetic, biological activity, and relationships between atacicept dose and Ig antibody response were evaluated. Pharmacokinetic profiles of atacicept were nonlinear, influenced by saturable binding with its ligands, but were consistent and predictable. Atacicept treatment reduced Ig and RF serum concentration. IgM antibody levels were most sensitive to atacicept, followed by IgA and IgG, underlining the biological activity of atacicept in patients with rheumatoid arthritis. These findings can be used to explore dosing regimen design scenarios in future studies.
An OspC-Specific Monoclonal Antibody Passively Protects Mice from Tick-Transmitted Infection by Borrelia burgdorferi B31 (1999)

A murine monoclonal antibody directed against Borrelia burgdorferi B31 outer surface protein C (OspC) antigen was generated by a method whereby borreliae were inoculated into the mouse via the natural transmission mode of tick feeding. Passive immunization with this antibody resulted in protection of C3H/HeJ and outbred mice from a tick-transmitted challenge infection. Immunofluorescence staining of borrelia cells indicated surface exposure of the OspC epitope reactive with the monoclonal antibody.
A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells. (1996)

Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might lead to novel approaches in immunotherapy. However, it has proven difficult to generate antibodies with the specificity of T cells by conventional hybridoma techniques. Here we report that the phage display technology is a feasible alternative to generate antibodies recognizing specific, predetermined peptide/MHC complexes.
Arterial Paclitaxel Distribution and Deposition (2000)

Successful implementation of local arterial drug delivery requires transmural distribution of drug. The physicochemical properties of the applied compound, which govern its transport and tissue binding, become as important as the mode of delivery. Hydrophilic compounds distribute freely but are cleared rapidly. Hydrophobic drugs, insoluble in aqueous solutions, bind to fixed tissue elements, potentially prolonging tissue residence and biological effect. Paclitaxel is such a hydrophobic compound, with tremendous therapeutic potential against proliferative vascular disease. We hypothesized that the recent favorable preclinical data with this compound may derive in part from preferential tissue binding as a result of unique physicochemical properties. The arterial transport of paclitaxel was quantified through application ex vivo and measurement of the subsequent transmural distribution. Arterial paclitaxel deposition at equilibrium varied across the arterial wall and was everywhere greater in concentration than in the applied drug source. Permeation into the wall increased with time, from 15 minutes to 4 hours, and varied with the origin of delivery. In contrast to hydrophilic compounds, the concentration in tissue exceeds the applied concentration and the rate of transport was markedly slower. Furthermore, endovascular and perivascular paclitaxel application led to markedly differential deposition across the blood vessel wall. These data suggest that paclitaxel interacts with arterial tissue elements as it moves under the forces of diffusion and convection and can establish substantial partitioning and spatial gradients across the tissue. The complexity of paclitaxel pharmacokinetics requires in-depth investigation if this drug is to reach its full clinical potential in proliferative vascular diseases.
Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group (1997)

A standardized serum bactericidal assay (SBA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines. We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SBA titers. The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera. The critical assay parameters for the reproducible measurement of SBA titers were found to include the target strain, assay incubation time, and complement. The resulting standardized SBA was used by 10 laboratories to measure functional anticapsular antibody against serogroup A strains F8238 and serogroup C strain C11. In the multilaboratory study, SBA titers were measured in duplicate for 14 pairs of sera (seven adults and seven children) before and after immunization with a quadrivalent polysaccharide (A, C, Y, and W-135) vaccine. The standardized SBA was reliable in all laboratories regardless of experience in performing SBAs. For most sera, intralaboratory reproducibility was +/- 1 dilution; interlaboratory reproducibility was +/- 2 dilutions. The correlation between median titers (interlaboratory) and enzyme-linked immunosorbent assay total antibody concentrations was high for both serogroup A (r = 0.86; P < 0.001; slope = 0.5) and serogroup C (n = 0.86; P < 0.001; slope = 0.7). The specified assay, which includes the critical parameters of target strain, incubation time, and complement source, will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines.
Between Wars (1990)

The signing of the armistice was the starting gun of a race for home. By Thanksgiving, 1918, more than half the weathermen were on the high seas bound for the states.KeywordsWeather BureauWeather ServiceGeneral StaffCanal ZoneSignal CorpsThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
The effect of dietary inclusion of yeast culture on digestion in the sheep (1990)

ABSTRACT Six mature sheep, each fitted with a rumen cannula, were assigned to six diets in a 6 × 6 Latin-square design experiment to examine the effects of a yeast culture on ruminal metabolism, rumen liquid outflow rate, fibre digestion in the rumen and overall nutrient digestibility. The yeast culture (YC) was a commercial product composed of a yeast ( Saccharomyces cerevisae ) and the media on which it grew and dried so as to maintain its fermentative capacity. The six dietary treatments were three diets differing in hay dry matter (DM): concentrate DM ratio (90: 10, 65: 35 and 40: 60 designated low, medium and high concentrate respectively) each given either without or with a supplement of 4 g/day of YC. Treatment periods were of 3 weeks duration. There were significant effects of dietary forage: concentrate ratio on rumen function ( P &lt; 0·05). Rumen pH, rumen liquid outflow rate, rumen ammonia concentration, total volatile fatty acids concentration, and molar proportions of acetate, propionate and butyrate were not significantly affected by the inclusion of YC ( P &lt; 0·05). Supplemental YC did not affect the overall nutrient digestibility of organic matter, neutral-detergent fibre or gross energy measured in vivo . However, at every forage:concentrate ratio, YC increased the disappearance of hay organic matter from nylon bags incubated in the rumen for 24 h ( P &lt; 0·05). The values with and without YC were 0·482 and 0·432 for the low, 0·423 and 0·366 for the medium, and 0·360 and 0·321 for the high concentrate diets respectively. However, YC had no effect on hay disappearance when bags were incubated for 48 h. YC appeared to increase the initial rate of forage digestion in the rumen without altering overall food digestibility or the patern of production of fermentation end products.
α7 Integrin Mediates Cell Adhesion and Migration on Specific Laminin Isoforms (1996)

The laminin-binding alpha7beta1 integrin receptor is expressed at high levels by skeletal and cardiac muscles and by certain melanocytic cells. We have assessed the potential role of the alpha7A/B integrin isoforms in mediating cell adhesion and motility and determined the laminin isoform specificity of this integrin. When MCF-7 breast carcinoma cells, normally nonadherent to laminin 1, were stably transfected with cDNA for mouse alpha7, they adhered with high efficiency and migrated on laminin 1 substrates. Function-perturbing monoclonal antibodies generated to mouse alpha7 subunit blocked both adhesion and migration of alpha7 transfectants on laminin 1 substrates. Additional studies with MCF-7 transfectants revealed that alpha7beta1 binds well to laminin 1 and to a mixture of laminin 2 and 4 but not to laminin 5. Importantly, alpha7beta1 was capable of promoting motility on both laminin 1 and laminin 2/4 substrates. However, MCF-7 cells transfected with cDNA for either alpha7A or alpha7B showed no significant differences in cell adhesion or motility on laminin 1 substrates. Although the role for the alternatively spliced cytoplasmic variants of alpha7 remains unknown, the results establish that alpha7beta1 mediates cell adhesive activities on a restricted number of laminin isoforms.
Quantitative Raman Reaction Monitoring Using the Solvent as Internal Standard (2005)

Despite its potential, the use of Raman spectroscopy for real-time quantitative reaction monitoring is still rather limited. The problems of fluorescence, laser instability, low intensities, and the inner filter effect often outscore the advantages as narrow bands, the use of glass fibers, and low scattering of water and glass. In this paper, we present real-time quantitative monitoring of the catalyzed Heck reaction by using the solvent as internal standard. In this way, all multiplicative distortions, e.g., laser intensity variations or absorbance of the laser light, can be corrected for. We also show that a limited amount of fluorescence does not hamper the analysis. Finally, we present a new method to correct for the inner filter effect, i.e., the absorbance of Raman scattered light by the reaction medium. Simultaneous absorption measurements of the reaction mixture enable accurate correction of Raman signals for the inner filter effect. Thus, for reaction monitoring applications, a Raman spectrometer should be equipped with an absorbance measurement device.
Low Cost and Low Weight Technologies for Planetary Surface Exploration (2007)

This paper presents the results of recent efforts towards the design of low cost and low weight technologies for autonomous vehicles. The test bench for such technologies is an autonomous ground vehicle (UGV) designed and built at University of Pisa. The main issues covered are related to guidance and navigation, by using an integrated system based on odometric and inertial sensors. The problem of obstacle recognition and avoidance is addressed by online vision-based algorithms, and compared with current methods (such as SLAM), presently used for this type of application. Cooperative localization and multi-vehicle coordination are also addressed using dynamic path allocation methods applied in the past to terrestrial unmanned air vehicles coordination and cooperative control. The proposed methodologies are validated through computer simulation, as well as via limited field experiments.
Immunotoxins that target an oncogenic mutant epidermal growth factor receptor expressed in human tumors. (1995)

Human cancers arise from a series of mutations, many of which direct the expression of mutant proteins with altered functions. These aberrant proteins are attractive targets for new therapeutic agents. One such protein is a mutant epidermal growth factor receptor (EGFRvIII) that has an in-frame deletion near the NH2 terminus of its extracellular domain. This protein was first identified in human gliomas, but has also been shown to be present in lung and breast carcinomas. The deletion results in a receptor with constitutive tyrosine kinase activity that enhances the tumorigenicity of glioblastomas in vivo. The deletion also creates a tumor-specific cell-surface sequence at the deletion junction. Three specific anti-EGFRvIII mAbs have been isolated following immunization with a mixture of a deletion junction synthetic peptide and EGFRvIII as present on cell membranes. We have constructed immunotoxins by conjugating a modified version of Pseudomonas exotoxin A to these mAbs. Immunotoxins were tested on cells that had been transfected with cDNA for the EGFRvIII receptor and expressed receptor protein at 5 x 10(5) receptors/cell. All three immunotoxins were cytotoxic to these cells, with 50% inhibition of protein synthesis occurring in a 15-50 pM range. The immunotoxins specifically targeted EGFRvIII, as their cytotoxicity could be blocked by their respective free antibody. They showed little or no cytotoxicity to cells expressing high levels of normal epidermal growth factor receptors, demonstrating that they are able to discriminate between cells expressing the mutant receptor and those expressing the wild-type receptor. Immunotoxins targeted to mutant epidermal growth factor receptors are promising candidates for further development as tumor cell-specific therapeutic agents.
Quantitative Immunocytofluorographic Analysis of CD4 Surface Antigen Expression and HIV Infection of Human Peripheral Blood Monocyte/Macrophages (1987)

HIV infection of CD4-bearing lymphocytes alone does not fully explain the immune dysfunction of AIDS. Monocyte/macrophages infected with HIV may serve as a reservoir of HIV, may function abnormally and may transmit infection to other susceptible cells, thus playing a central role in the development of the immunodeficiency of AIDS. Quantitative analysis of surface antigens and measurement of HIV antigens in infected cells have been difficult using the conventional approach of immunofluorescent staining of cells on slides. We have developed a system that maintains monocyte/macrophages in suspension culture for at least four months. Through immunocytofluorographic single cell analysis we have shown that CD4 antigen is present on monocytes, and that a tenfold increase in expression occurs during the first two weeks in culture. In contrast, LeuM3 antigens decreased to background levels in the course of long-term culture. Using anti-HIV p24 antibody, we have demonstrated that monocyte/macrophages can be infected with HIV. Up to 70% of cells from individual donors could be infected. The techniques herein described allow in vitro quantitation of some of the mechanisms by which HIV infection of monocyte/macrophages may contribute to the immunodeficiency states associated with AIDS.
Enhancement of Vaccine-induced Primary and Memory CD8+ T-cell Responses by Soluble PD-1 (2011)

Programmed death 1 (PD-1) signaling through its ligands, PD-L1 and PD-L2, has been known to negatively regulate T-cell responses. In addition, PD-L1 has been shown to interact with B7-1 costimulatory molecule to inhibit T-cell responses. Extensive studies have shown that PD-1/PD-L blockade restores exhausted T cells during chronic viral infections and tumors. In this study, we evaluated the effects of soluble PD-1 (sPD-1) as a blockade of PD-1 and PD-L1 on vaccine-elicited antigen-specific T-cell responses in mice. Coadministration of sPD-1 DNA with human papilloma virus-16 E7 DNA vaccine significantly enhanced E7-specific CD8(+) T-cell responses, resulting in potent antitumor effects against E7-expressing tumors. We also found that sPD-1, codelivered with adenovirus-based vaccine, could increase antigen-specific CD8(+) T-cell responses, indicating vaccine type-independent adjuvant effect of sPD-1. In addition, the frequency and functional activity of adoptively transferred OT-I cells, particularly memory CD8(+) T cells, were augmented by coadministration of sPD-1 DNA, which was closely associated with increased T-cell proliferation and reduced T-cell apoptosis through upregulation of Bcl-xL expression during T-cell activation. Codelivery of sPD-1 DNA also enhanced maturation of dendritic cells (DCs) in vivo which was accompanied by upregulation of DC maturation markers such as major histocompatibility complex class II. Taken together, our findings show that sPD-1 potently enhances codelivered antigen-specific CD8(+) T-cell responses and in vivo maturation of DCs during activation of naive CD8(+) T cells, suggesting that an immunization strategy with sPD-1 as an adjuvant can be used to increase antigen-specific T-cell immunity elicited by vaccination.
Conformal Coating of Thin Polymer Electrolyte Layer on Nanostructured Electrode Materials for Three-Dimensional Battery Applications (2010)

Various three-dimensional (3D) battery architectures have been proposed to address effective power delivery in micro/nanoscale devices and for increasing the stored energy per electrode footprint area. One step toward obtaining 3D configurations in batteries is the formation of core-shell nanowires that combines electrode and electrolyte materials. One of the major challenges however in creating such architectures has been the coating of conformal thin nanolayers of polymer electrolytes around nanostructured electrodes. Here we show conformal coatings of 25-30 nm poly(methyl methacralate) electrolyte layers around individual Ni-Sn nanowires used as anodes for Li ion battery. This configuration shows high discharge capacity and excellent capacity retention even at high rates over extended cycling, allowing for scalable increase in areal capacity with electrode thickness. Our results demonstrate conformal nanoscale anode-electrolyte architectures for an efficient Li ion battery system.
Intertwining of thrombosis and inflammation in atherosclerosis (2007)

New research has identified signaling pathways that intertwine thrombotic and inflammatory pathways with the development and progression of atherosclerosis. These signaling pathways contain positive feedback loops that propagate atherogenesis. Targeting molecular regulators at the interface of thrombosis and inflammation simultaneously may reduce thrombosis and inflammation, thus breaking pathological cycles that promote atherosclerosis and associated thrombotic complications.
IL-10 Released by Concomitant TLR2 Stimulation Blocks the Induction of a Subset of Th1 Cytokines That Are Specifically Induced by TLR4 or TLR3 in Human Dendritic Cells (2004)

Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated with agonists of TLR2, TLR3, TLR4, TLR5, and TLR7, first individually and then in combination. Several cytokines were equally induced by all TLR agonists, but four genes, IFN-beta, IFN-gamma-inducible protein 10 (IP-10), IL-12p35, and IL-15, showed a very restricted pattern of induction. Thus, each TLR appears to possess a distinctive ability to activate DCs or PBMCs, suggesting that TLR-mediated responses cannot be simply cataloged as resembling either TLR2 (MyD88 dependent) or TLR4 (MyD88 independent) and that other signaling modalities may exist. The analysis of DC and PBMC activation by combinations of TLR agonists revealed that TLR2 agonists are able to block the induction of IP-10, IL-12p35, and IFN-gamma, but not IL-15 and IFN-beta, by TLR3 and TLR4. TLR2 stimulation led to rapid release of IL-10 that is responsible for inhibition of IP-10 and IL-12p35 induction. Cross-talk between different TLRs may modify the primary responses of TLR to their agonist, adding a further level of complexity to the regulation of innate immunity.
[Expression of CCR6 and CCR7 in laryngeal squamous cell carcinoma]. (2010)

CCR6 and CCR7 are expressed in tumor situ, metastatic LN and PBMC,and might exert a potential role in LSCC development.
Laser-induced fluorescence imaging of subsurface tissue structures with a volume holographic spatial-spectral imaging system (2008)

A three-dimensional imaging system incorporating multiplexed holographic gratings to visualize fluorescence tissue structures is presented. Holographic gratings formed in volume recording materials such as a phenanthrenquinone poly(methyl methacrylate) photopolymer have narrowband angular and spectral transmittance filtering properties that enable obtaining spatial-spectral information within an object. We demonstrate this imaging system's ability to obtain multiple depth-resolved fluorescence images simultaneously.
Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. (1991)

The expression of interleukin (IL) 2, IL-4, IL-10, and interferon gamma (IFN-gamma) by lymphocyte subsets was examined during infection of resistant C57BL/6 and susceptible BALB/c mice with the protozoan parasite Leishmania major. CD4+ and CD8+ T lymphocytes and B lymphocytes were isolated from the lymph nodes draining infectious lesions, and their RNA was examined for lymphokine transcripts. Distinct patterns of CD4+ cell cytokine expression were apparent: C57BL/6 CD4+ cells contained IFN-gamma and IL-2 mRNA, whereas BALB/c CD4+ cells expressed IL-4 and IL-10 message. CD8+ cells contributed little lymphokine expression during disease, but B cells were a major source of IL-2 mRNA in both strains of mice. BALB/c mice made resistant by treatment with anti-CD4 antibody at the time of infection repopulated lymph nodes with CD4+ cells that expressed IL-2 and IFN-gamma. Protective treatment with anti-IL-4 antibody in vivo also resulted in the appearance of CD4+ cells with increased IFN-gamma and diminished IL-4 and IL-10 expression. These data establish CD4+ cells as the primary source of IFN-gamma in healing mice and of IL-4 and IL-10 during progressive infection and confirm that the spectral extremes of this disease are characterized by the presence of CD4+ cells expressing Th1 or Th2 phenotypes in vivo.