gebhart/patrepeval huggingface dataset:
Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity. (1988)

Immunization of DBA/1 mice with type II collagen resulted in typical and progressive arthritis, which is associated with the production of high titer of anti-collagen antibody and the induction of cell-mediated immunity as exemplified by delayed type hypersensitivity response as well as lymphokine production. In contrast, administration of heat-denatured collagen into DBA/1 mice failed to induce the arthritis. These mice produced only marginal antibody, whereas they developed comparable cell-mediated immunity to that induced by immunization with native collagen, and therefore the inoculation of heat-denatured collagen provided the regimen capable of inducing preferentially cell-mediated immunity without the generation of high level of antibody. Inasmuch as administration of antibody induced only marginal and transient joint swelling not associated with typical histologic lesion, the synergistic effect of humoral and cell-mediated immunities was investigated using antibody preparation and the regimen to induce selectively cell-mediated immunity. The results demonstrate that administration of antibody into DBA/1 mice pre-sensitized with heat-denatured collagen resulted in potent and progressive arthritis. Such synergy was further confirmed by the induction of arthritis in T cell-depleted DBA/1 mice that had been adoptively transferred with antibody and lymphoid cells from heat-denatured collagen-sensitized mice. Moreover, it was revealed that the nature of cells capable of transferring cell-mediated immunity was of Thy-1+ and L3T4+ Lyt-2-. These results indicate that anti-collagen antibody and L3T4+ T cell-mediated cellular immunity are crucially required for the perpetuated development of type II collagen-induced arthritis.
The kinase inhibitors Sunitinib and Sorafenib differentially affect reactivity of NK cells against Renal Cell Cancer (2008)

Sunitinib and Sorafenib are multi‐kinase inhibitors licensed for the treatment of patients with advanced renal cell cancer (RCC) and target, among others, VEGF receptors, PDGF receptors, c‐kit and Flt3. Beyond that, Sorafenib inhibits c‐RAF and B‐RAF. Here we report that Sorafenib but not Sunitinib significantly (p&lt;0.05, Mann‐Whitney U‐test) reduce cell surface CD107a expression (about 50%) on NK cells as a surrogate marker for degranulation in response to tumor targets. In line, pharmacological levels of Sorafenib but not Sunitinib significantly (p&lt;0.05) diminish cytotoxicity of primary NK cells against the RCC cell lines A498, ACHN and CAKI‐2 (46% to 14%, 52% to 22% and 63% to 42%, respectively) in chromium release assays. While Sunitinib had no effect, Sorafenib, alike the specific c‐RAF inhibitor ZM336372 or the specific MEK inhibitor PD98059, markedly reduces ERK phosphorylation which regulates the movement of lytic granula towards target cells. Our results indicate that NK cell anti‐tumor reactivity is impaired by Sorafenib but not by Sunitinib due to the additional inhibitory effect of Sorafenib on the ERK pathway, which has been demonstrated to dictate NK cell cytotoxicity. We therefore conclude that Sunitinib is exquisitely suitable for combination with immunotherapeutic approaches in RCC patients.
Evaluation of Magnetic Beads Agitation Performance Operated by Multi-Layered Flat Coils (2007)

We have previously proposed a magnetic bead handling mechanism for micro-total-analysis-systems and have developed a palmtop-sized biochemical analysis system. Appropriate agitation is one of the crucial issues in micro-meter-sized fluidic systems. We investigated the agitation produced by using multilayered flat coils and magnetic beads. The beads were magnetically agitated inside the droplet by changing the external magnetic field distribution, and the agitation performance was evaluated by using an enzymatic reaction. The reaction efficiency increased linearly with an increase in the reaction time and was more than four times as efficient with agitation than without agitation.
Hepatitis B Virus (HBV) Virion and Covalently Closed Circular DNA Formation in Primary Tupaia Hepatocytes and Human Hepatoma Cell Lines upon HBV Genome Transduction with Replication-Defective Adenovirus Vectors (2001)

Hepatitis B virus (HBV), the causative agent of B-type hepatitis in humans, is a hepatotropic DNA-containing virus that replicates via reverse transcription. Because of its narrow host range, there is as yet no practical small-animal system for HBV infection. The hosts of the few related animal viruses, including woodchuck hepatitis B virus and duck hepatitis B virus, are either difficult to keep or only distantly related to humans. Some evidence suggests that tree shrews (tupaias) may be susceptible to infection with human HBV, albeit with low efficiency. Infection efficiency depends on interactions of the virus with factors on the surface and inside the host cell. To bypass restrictions during the initial entry phase, we used recombinant replication-defective adenovirus vectors, either with or without a green fluorescent protein marker gene, to deliver complete HBV genomes into primary tupaia hepatocytes. Here we show that these cells, like the human hepatoma cell lines HepG2 and Huh7, are efficiently transduced by the vectors and produce all HBV gene products required to generate the secretory antigens HBsAg and HBeAg, replication-competent nucleocapsids, and enveloped virions. We further demonstrate that covalently closed circular HBV DNA is formed. Therefore, primary tupaia hepatocytes support all steps of HBV replication following deposition of the genome in the nucleus, including the intracellular amplification cycle. These data provide a rational basis for in vivo experiments aimed at developing tupaias into a useful experimental animal system for HBV infection.
Recombinant Parainfluenza Virus 5 Vaccine Encoding the Influenza Virus Hemagglutinin Protects against H5N1 Highly Pathogenic Avian Influenza Virus Infection following Intranasal or Intramuscular Vaccination of BALB/c Mice (2012)

New approaches for vaccination to prevent influenza virus infection are needed. Emerging viruses, such as the H5N1 highly pathogenic avian influenza (HPAI) virus, pose not only pandemic threats but also challenges in vaccine development and production. Parainfluenza virus 5 (PIV5) is an appealing vector for vaccine development, and we have previously shown that intranasal immunization with PIV5 expressing the hemagglutinin from influenza virus was protective against influenza virus challenge (S. M. Tompkins, Y. Lin, G. P. Leser, K. A. Kramer, D. L. Haas, E. W. Howerth, J. Xu, M. J. Kennett, J. E. Durbin, R. A. Tripp, R. A. Lamb, and B. He, Virology 362:139-150, 2007). While intranasal immunization is an appealing approach, PIV5 may have the potential to be utilized in other formats, prompting us to test the efficacy of rPIV5-H5, which encodes the HA from H5N1 HPAI virus, in different vaccination schemes. In the BALB/c mouse model, a single intramuscular or intranasal immunization with a live rPIV5-H5 (ZL46) rapidly induced robust neutralizing serum antibody responses and protected against HPAI challenge, although mucosal IgA responses primed by intranasal immunization more effectively controlled virus replication in the lung. The rPIV5-H5 vaccine incorporated the H5 HA into the virion, so we tested the efficacy of an inactivated form of the vaccine. Inactivated rPIV5-H5 primed neutralizing serum antibody responses and controlled H5N1 virus replication; however, similar to other H5 antigen vaccines, it required a booster immunization to prime protective immune responses. Taken together, these results suggest that rPIV5-HA vaccines and H5-specific vaccines in particular can be utilized in multiple formats and by multiple routes of administration. This could avoid potential contraindications based on intranasal administration alone and provide opportunities for broader applications with the use of a single vaccine vector.
Oxygen, Oxidants, and Antioxidants in Wound Healing (2002)

Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality of wound care is of outstanding interest, it clearly lacks the support of mechanism-oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst-derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for "natural remedies" has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.
Accessing the tonotopic organization of the ventral cochlear nucleus by intranuclear microstimulation (1998)

This study is part of a program to develop an auditory prosthesis for the profoundly deaf, based on multichannel microstimulation in the cochlear nucleus. The functionality of such a device is dependent on its ability to access the tonotopic axis of the human ventral cochlear nucleus in an orderly fashion. In these studies, we utilized the homologies between the human and feline ventral cochlear nuclei and the known tonotopic organization of the central nucleus of the inferior colliculus (IC). In anesthetized cats, stimuli were delivered to three or four locations along the dorsal-to-ventral axis of the posteroventral cochlear nucleus (PVCN), and for each stimulus location, we recorded the multiunit neuronal activity and the field potentials at 20 or more locations along the dorsolateral-ventromedial (tonotopic) axis of the IC. The current source-sink density (CSD), which delimits regions of neuronal activity, was computed from the sequence of field potentials recorded along this axis. The multiunit activity and the CSD analysis both showed that the tonotopic organization of the PVCN can be accessed in an orderly manner by intranuclear microstimulation in several regions of the PVCN, using the range of stimulus pulse amplitudes that have been shown in previous studies to be noninjurious during prolonged intranuclear microstimulation via chronically implanted microelectrodes. We discuss the applicability of these findings to the design of clinical auditory prostheses for implantation into the human cochlear nucleus.
Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis (1999)

Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large ORFs encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3, and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 homologous sets of enzyme activities (modules), each catalyzing a specific round of polyketide chain elongation. The clustered genes encoding polyketide synthase are organized as two sets of six modular repeats, aveA1-aveA2 and aveA3-aveA4, which are convergently transcribed. The total of 55 constituent active sites makes this the most complex multifunctional enzyme system identified to date. The sequenced DNA region contains 14 additional ORFs, some of which encode polypeptides governing other key steps in avermectin biosynthesis. Between the two sets of polyketide synthase genes lie two genes involved in postpolyketide modification, one of which encodes cynthochrome P450 hydroxylase that probably catalyzes furan ring formation at C6 to C8a. Immediately right of the large polyketide synthase genes is a set of genes involved in oleandrose biosynthesis and its transglycosylation to polyketide-derived aglycons. This cluster includes nine genes, but one is not functional in the biosynthesis of avermectin. On the left side of polyketide synthase genes, two ORFs encoding methyltransferase and nonpolyketide synthase ketoreductase involved in postpolyketide modification are located to the left of the polyketide synthase genes, and an adjacent gene encodes a regulatory function that may be involved in activation of the transcription of avermectin biosynthetic genes.
Structure and activation of C1, the complex initiating the classical pathway of the complement cascade (2017)

The complement system is an important antimicrobial and inflammation-generating component of the innate immune system. The classical pathway of complement is activated upon binding of the 774-kDa C1 complex, consisting of the recognition molecule C1q and the tetrameric protease complex C1r<sub>2</sub>s<sub>2</sub>, to a variety of activators presenting specific molecular patterns such as IgG- and IgM-containing immune complexes. A canonical model entails a C1r<sub>2</sub>s<sub>2</sub> with its serine protease domains tightly packed together in the center of C1 and an intricate intramolecular reaction mechanism for activation of C1r and C1s, induced upon C1 binding to the activator. Here, we show that the serine protease domains of C1r and C1s are located at the periphery of the C1r<sub>2</sub>s<sub>2</sub> tetramer both when alone or within the nonactivated C1 complex. Our structural studies indicate that the C1 complex adopts a conformation incompatible with intramolecular activation of C1, suggesting instead that intermolecular proteolytic activation between neighboring C1 complexes bound to a complement activating surface occurs. Our results rationalize how a multitude of structurally unrelated molecular patterns can activate C1 and suggests a conserved mechanism for complement activation through the classical and the related lectin pathway.
Spectrum-blind reconstruction of multi-band signals (2008)

We develop a perfect reconstruction scheme from point-wise sub-Nyquist rate samples for multi-band signals. Our approach is blind, namely the knowledge of the band locations is not used in the design of either the sampling or the reconstruction stage. This is in contrast to previous approaches to reconstruct this class of signals, which required information about the spectral support at least in the reconstruction stage. Our scheme guarantees exact recovery for a wide class of multi-band signals without the use of heuristics or discretization methods.
Measurement and analysis of the indoor radio channel in the frequency domain (1990)

Using a network analyzer, several experiments for the frequency-domain characterization of the indoor radio channel in the 0.9-1.1-GHz band are performed. In the experiments, the frequency response measurements are taken at spatially distributed locations throughout the test area by fixing the receiver in a central location and moving the transmitter to different locations. The experiments are performed in a high-rise office building and a three-story building with offices and laboratories. For each experiment, the exponent of the power-distance relationship and the statistics of the 3-dB width of the frequency correlation function are determined from the frequency-domain data. The approximation to the impulse response of the channel is obtained from the inverse Fourier transform of the frequency response. An empirical exponential relationship between the 3-dB width of the frequency correlation function and the inverse of the RMS (root mean square) delay spread of the impulse response is derived.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thymic Endocrinology (1998)

The thymus involutes relatively early in life; cellular immune deficiencies of aging correspond to decline in function of the hypothalamic-pituitary-endocrine axis. Recent studies point to important roles for the pituitary, the pineal, and the autonomic nervous system as well as the thyroid, gonads and adrenals in the thymus integrity and function. Thymic function at the local level requires complex cellular interactions among thymic stromal cells and developing thymocytes involving paracrine and autocrine mediators including interleukins (ILs) 1, 2, 6, 7, 8, colony-stimulating factors (CSFs), interferon-gamma, thymosin alpha 1, and zinc-thymulin. An important endocrine function of the thymus is to package zinc in zinc-thymulin for delivery to the periphery. Thymic involution has been treated with interleukins, thymic hormones, growth hormone, prolactin, melatonin, zinc, and others. Our work to reverse thymic involution in hydrocortisone-treated, aged mice with interleukins, thymosin alpha 1, and zinc will be reviewed. Recent efforts to treat successfully immune deficiency in aged and cancer-bearing humans will be presented.
Specific wetting probed with biomimetic emulsion droplets (2008)

We have produced emulsion droplets of controlled size and composition coated by ligands, and studied the adhesion of these drops on a solid substrate coated by receptors and polymers. Using transmission, RICM and fluorescence microscopy we assess the size, contact angle and ligand density for each drop. We first show that non-specific interactions significantly enhance the proteins density within the adhesive patch. Then we show that binding within the patch is partially inhibited in good agreement with the hypothesis of an absence of translational diffusion. We confirm that the density of specific bonds sets the adhesive energy and therefore the final contact angle, and finally show that specific binding in our system is always associated with the existence of a positive line tension, which linearly increases with the density of receptors. These experiments describe a new scenario for specific wetting which raises the importance of the coupling between non-specific interactions and specific binding.
Self‐(Un)rolling Biopolymer Microstructures: Rings, Tubules, and Helical Tubules from the Same Material (2015)

We have demonstrated the facile formation of reversible and fast self-rolling biopolymer microstructures from sandwiched active-passive, silk-on-silk materials. Both experimental and modeling results confirmed that the shape of individual sheets effectively controls biaxial stresses within these sheets, which can self-roll into distinct 3D structures including microscopic rings, tubules, and helical tubules. This is a unique example of tailoring self-rolled 3D geometries through shape design without changing the inner morphology of active bimorph biomaterials. In contrast to traditional organic-soluble synthetic materials, we utilized a biocompatible and biodegradable biopolymer that underwent a facile aqueous layer-by-layer (LbL) assembly process for the fabrication of 2D films. The resulting films can undergo reversible pH-triggered rolling/unrolling, with a variety of 3D structures forming from biopolymer structures that have identical morphology and composition.
Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine (1976)

A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity of the 1-methyl-3-isobutylxanthine (MIX) structure for one of the two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography of the soluble fraction of the intima + media layer of pig coronary arteries. A series of 1,3-dialkyluracils was of low potency as inhibitors of either peak I or peak II. The 7-substituted xanthines were prepared by alkylation of MIX with the corresponding alkyl or aralkyl halide in DMF containing K2CO3. These compounds were, in general, much less potent inhibitors of peak II activity than was MIX, but some of them retained the potency of MIX as inhibitors of peak I and, therefore, were relatively specific for inhibition of peak I. 7-Bzl-MIX was the most selective compound tested; it was a potent inhibitor of peak I activity but was much less effective as an inhibitor of peak II activity. Substitution of either electron-withdrawing (nitro) or electron-donating (methoxy) groups on the 7-benzyl moiety reduced the effectiveness of the 7-benzyl compounds as inhibitors of peak I. Chlorobenzyl substitution increased the potency slightly over the benzyl but not the selectivity between peaks.
The isolation and detection of Escherichia coli O157 by use of immunomagnetic separation and immunoassay procedures (1996)

The use of immunomagnetic separation (IMS) techniques has been reported to reduce the total test time, and improve the sensitivity, of microbiological tests done on foods. This approach is being adopted in epidemiological investigations into suspected foodborne outbreaks of Escherichia coli O157 infection and has gained acceptance by public health laboratories and the food industry. This study demonstrated the ability of a commercially available IMS procedure, Dynabeads anti-E. coli O157, to enable detection of a few cells of E. coli O157 in 25 g of inoculated minced beef, giving results 1 d earlier than a cultural analysis of similar sensitivity. With correct choice of enrichment broths, IMS may increase isolation rate of E. coli O157 compared to that obtained using conventional cultural methods. It is suggested that this may be due to an increase in relative concentration of E. coli O157 compared with the background microflora present in minced beef, which may reduce reliability of non-IMS detection procedures by masking or mimicking target cells on selective/differential solid media. The use of an immunoassay incorporating an IMS step, EHEC-Tek (Organon-Teknika), enabled detection of a few cells of E. coli O157 in 25 g of minced beef. Comparison of the IMS-ELISA with a standard ELISA procedure (Tecra) indicated the sensitivity of the latter system to be greater, perhaps resulting in the higher isolation rate. The use of a method to reliability isolate and detect extremely low levels of E. coli O157 in a food is necessary to aid reduction in the incidence of this most serious of foodborne pathogens.
Water-in-Carbon Dioxide Microemulsions: An Environment for Hydrophiles Including Proteins (1996)

Carbon dioxide in the liquid and supercritical fluid states is useful as a replacement for toxic organic solvents. However, nonvolatile hydrophilic substances such as proteins, ions, and most catalysts are insoluble. This limitation was overcome by the formation of aqueous microemulsion droplets in a carbon dioxide-continuous phase with a nontoxic ammonium carboxylate perfluoropolyether surfactant. Several spectroscopic techniques consistently indicated that the properties of the droplets approach those of bulk water. The protein bovine serum albumin (BSA) with a molecular weight of 67,000 is soluble in this microemulsion and experiences an environment similar to that of native BSA in buffer.