gebhart/patrepeval huggingface dataset:
Chimeric influenza viruses incorporating epitopes of outer membrane protein F as a vaccine against pulmonary infection with Pseudomonas aeruginosa. (1997)

Peptide 10 (NATAEGRAINRRVE, residues 305-318 of mature protein F) is one of two linear B-cell epitopes within outer membrane protein F of Pseudomonas aeruginosa both of which have been shown to elicit whole cell-reactive antibodies and to afford protection in animal models against P. aeruginosa infection. Influenza A virus was chosen as a vector to present this epitope in a human-compatible vaccine. Various lengths of the peptide 10 epitope ranging from a 5-mer (GRAIN), 7-mer (AINRRVE), 8-mer (TAEGRAIN), 9-mer (GRAINRRVE), 11-mer (AEGRAINRRVE) to a 12-mer (TAEGRAINRRVE) were attempted to be presented into the antigenic B-site of the hemagglutinin (HA) of live recombinant influenza virus. Using PCR, DNA sequences encoding these various peptide 10 lengths were inserted into the HA gene of influenza A/WSN/33 virus. By using a reverse-genetics transfection system, RNA transcribed in vitro from these chimeric HA genes was reassorted into infectious virus. To date chimeric viruses have been rescued and purified containing the peptide 10 5-mer, 7-mer, 8-mer, and 11-mer. RT-PCR and sequencing have confirmed the presence of P. aeruginosa sequences in the HA RNA segment of each chimeric virus. Each of the four chimeric viruses produced to date was used to immunize mice to determine the ability of each chimeric virus to elicit antibodies reactive with whole cells of P. aeruginosa. The immunization protocol consisted of a series of three intranasal inoculations, followed by two intramuscular injections of the chimeric virus. The chimeric virus incorporating the 11-mer elicited IgG antibodies that reacted with various immunotype strains of P. aeruginosa in a whole cell ELISA at titers of 80 to 2,560, whereas the chimeric virus incorporating the 8-mer elicited whole cell-reactive IgG antibodies at titers of 320 to 2,560. These data suggest that these two chimeric viruses may have vaccine efficacy against P. aeruginosa infection. These studies may result in the development of a chimeric influenza virus-protein F vaccine which would prove to be suitable for use in children with cystic fibrosis for the prevention of pulmonary colonization of these children with P. aeruginosa.
Directed combinatorial chemistry. (1996)

Combinatorial chemistry has given chemists access to vast numbers of molecules, but selecting the right one has proved more difficult. As chemists have gained experience in the technique, however, it has become possible to use solid- or solution-phase syntheses with different chemistries and scaffolds to produce libraries tailor-made for finding or optimizing a lead directed at almost any class of target.
Effects of Respiratory Alkalosis and Acidosis on Myocardial Blood Flow and Metabolism in Patients with Coronary Artery Disease (1998)

In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.
Effect of temperature on the size of Escherichia coli cells (1975)

The distributions of cell volumes of steady-state Escherichia coli ML30G cultures at various temperatures were measured. For cultures in a minimal medium, the distributions were indistinguishable at several temperatures between 15 and 30 C; at higher temperatures the cells were slightly smaller, and at lower temperatures they were slightly larger. For cultures in a complex medium, the cells were slightly larger at both high and low temperatures of growth. An abrupt change of temperature within the middle range led to a transient change in the distribution of cell volume, suggesting that the size of dividing cells is well regulated. No synchrony of division was induced by a change in temperature.
Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells (2014)

Adjuvant System AS01 is a liposome-based vaccine adjuvant containing 3-O-desacyl-4'-monophosphoryl lipid A and the saponin QS-21. AS01 has been selected for the clinical development of several candidate vaccines including the RTS,S malaria vaccine and the subunit glycoprotein E varicella zoster vaccine (both currently in phase III). Given the known immunostimulatory properties of MPL and QS-21, the objective of this study was to describe the early immune response parameters after immunization with an AS01-adjuvanted vaccine and to identify relationships with the vaccine-specific adaptive immune response. Cytokine production and innate immune cell recruitment occurred rapidly and transiently at the muscle injection site and draining lymph node postinjection, consistent with the rapid drainage of the vaccine components to the draining lymph node. The induction of Ag-specific Ab and T cell responses was dependent on the Ag being injected at the same time or within 24 h after AS01, suggesting that the early events occurring postinjection were required for these elevated adaptive responses. In the draining lymph node, after 24 h, the numbers of activated and Ag-loaded monocytes and MHCII(high) dendritic cells were higher after the injection of the AS01-adjuvanted vaccine than after Ag alone. However, only MHCII(high) dendritic cells appeared efficient at and necessary for direct Ag presentation to T cells. These data suggest that the ability of AS01 to improve adaptive immune responses, as has been demonstrated in clinical trials, is linked to a transient stimulation of the innate immune system leading to the generation of high number of efficient Ag-presenting dendritic cells.
Induction of Pyk-2

Fhosphorylation

During Lfa-l/Icam-1-Dependent Homotypic Adhesion of Fresh Human B-Cells (2000)

Stimulation with the combination of PDB plus ionomycin induced LFA-l/ICAM-1-dependent homotypic adhesion of tonsil B cells. Adhesion of tonsil B cells in our system induced tyrosine phosphorylation of Pyk-2. Disruption of homotypic adhesion and concomitant inhibition of induction of protein tyrosine phosphorylation was achieved by physical separation of the cells and by treatment with methyl-2,5-dihydroxycinnamate (MDHC), an inhibitor of protein tyrosine phosphorylation. These results suggest that protein tyrosine phosphorylation that is associated with homotypic adhesion is mediated by LFA-l/ICAM-1 interactions.
The Effects of Knock on the Hydrocarbon Emissions of a Spark-Ignition Engine (1969)

&lt;div class="htmlview paragraph"&gt;To determine the effects of knock in a spark-ignition, single-cylinder engine with cooled exhaust upon the exhaust composition, exhaust products (CO, CO&lt;sub&gt;2&lt;/sub&gt;, and total hydrocarbons) were measured by non-dispersive infrared analyzers (NDIRA) and by a flame ionization detector (FID). Individual hydrocarbons were separated on a gas-liquid chromatograph.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;In fuel-rich mixtures, the FID indicated noticible decreases in the hydrocarbon concentrations in the presence of knock. The NDIRA did not indicate a decrease in the hydrocarbons at knock of lower intensities but showed decreases in hydrocarbons at knock of higher intensities. Chromatograms indicated a preferential decreases in acetylene at the time of knock, causing different responses at lower intensities. In fuel-lean mixtures, no apparent effect of knock on the hydrocarbons was indicated.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Thus, it was concluded that in fuel-rich to stoichiometric regions, knock generally decreases the hydrocarbon concentration in the exhaust and the extent of the decreases is greater with the intensity of knock.&lt;/div&gt;
Immunologic Mechanisms in the Pathogenesis of Rheumatoid Arthritis (2005)

Although much is known about the etiology and pathogenesis of rheumatoid arthritis (RA), our understanding of the immune pathways remains incomplete. The observed clinical and pathologic manifestations result from activation of several interrelated immune pathways. Current concepts of RA pathogenesis, supported by animal models, laboratory studies, and clinical observation, have reestablished and revised some of the original views. Early proposals emphasized the importance of autoantibodies and immune complexes in the initiation of RA, suggested a role for T cells in the inflammatory response characteristic of RA, and based disease perpetuation on an imbalance in the cytokine networks. We now recognize that each of these interrelated mechanisms significantly contributes to RA pathogenesis, including T cells that can help initiate and perpetuate the disease. This article reviews the major components and immune pathways involved in RA and briefly discusses the animal models that contribute to our understanding. Although a unified theory of RA pathogenesis may not be possible at this time, a paradigm is presented that considers the immune pathways that contribute to disease progression and joint destruction. These pathways may have important implications for treatment, because their modulation by biologic response modifiers (BRMs) directed toward specific targets provides benefits to patients with RA. BRMs are a new class of therapeutic agents derived from biologically active molecules and designed to modulate specific immune or inflammatory pathways. Although currently approved BRMs still have limitations, choosing an appropriate target, possibly early rather than late in the immune response, might result in new and improved therapies for RA.
A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans (2001)

The Deleted in AZoospermia (DAZ) genes encode potential RNA-binding proteins that are expressed exclusively in prenatal and postnatal germ cells and are strong candidates for human fertility factors. Here we report the identification of an additional member of the DAZ gene family, which we have called BOULE. With the identification of this gene, it is clear that the human DAZ gene family contains at least three members: DAZ, a Y-chromosome gene cluster that arose 30-40 million years ago and whose deletion is linked to infertility in men; DAZL, the "father" of DAZ, a gene that maps to human chromosome 3 and has homologs required for both female and male germ cell development in other organisms; and BOULE, a gene that we propose is the "grandfather" of DAZ and maps to human chromosome 2. Human and mouse BOULE resemble the invertebrate meiotic regulator Boule, the proposed ortholog of DAZ, in sequence and expression pattern and hence likely perform a similar meiotic function. In contrast, the previously identified human DAZ and DAZL are expressed much earlier than BOULE in prenatal germ stem cells and spermatogonia; DAZL also is expressed in female germ cells. These data suggest that homologs of the DAZ gene family can be grouped into two subfamilies (BOULE and DAZL) and that members of the DAZ family evolved from an ancestral meiotic regulator, Boule, to assume distinct, yet overlapping, functions in germ cell development.
Regulation of Folding and Photochromic Reactivity of Terarylenes through a Host–Guest Interaction (2011)

The photochromic reactivity of terarylenes is integrated with molecular folding that is controlled through a host-guest interaction. A thieno[3,2,b]pyridine unit is introduced into a photochromic terarylene structure as an aryl unit to form a guest-interacting site. Thienopyridine-containing terarylenes showed solvent-dependent photochromic reactivity in solution. A terarylene moiety that contains two thienopyridyl units showed significantly high photocoloration reactivity as high as 88% of photocyclization quantum yield in methanol, whereas that value was only 24% in hexane. A temperature-dependent (1)H NMR spectroscopic study in different solvents indicated an interconversion between photochromic-reactive and unreactive conformations. In methanol, the intermolecular interaction between terarylene species and the solvent molecule slows the rate of interconversion and increases the population of the photochromic-active form, whereas the unreactive conformation is dominant in hexane. Crystal-structural studies demonstrated the perfect regulation of molecular folding between a photochromic-active form and an unreactive conformation by changing the solvents for recrystallization. Single crystals prepared from solutions in methanol showed reversible photochromic reactivity, whereas recrystallization from solutions in hexane did not show this reactivity. X-ray crystallographic studies of single crystals from solutions in methanol demonstrated that the photochromic molecules bind a solvent methanol molecule at the guest-interacting site to regulate the molecular conformation into a photochromic-active form in collaboration with specific intramolecular interactions, whereas crystals from solutions in hexane possess the photochromic-unreactive conformation.
Potent bronchoprotective effect of deep inspiration and its absence in asthma (2000)

In the absence of deep inspirations, healthy individuals develop bronchoconstriction with methacholine inhalation. One hypothesis is that deep inspiration results in bronchodilation. In this study, we tested an alternative hypothesis, that deep inspiration acts as a bronchoprotector. Single-dose methacholine bronchoprovocations were performed after 20 min of deep breath inhibition, in nine healthy subjects and in eight asthmatics, to establish the dose that reduces forced expiratory volume in 1 s by >15%. The provocation was repeated with two and five deep inspirations preceding methacholine. Additional studies were carried out to assess optimization and reproducibility of the protocol and to rule out the possibility that bronchoprotection may result from changes in airway geometry or from differential spasmogen deposition. In healthy subjects, five deep inspirations conferred 85% bronchoprotection. The bronchoprotective effect was reproducible and was not attributable to increased airway caliber or to differential deposition of methacholine. Deep inspirations did not protect the bronchi of asthmatics. We demonstrated that bronchoprotection is a potent physiologic function of lung inflation and established its absence, even in mild asthma. This observation deepens our understanding of airway dysfunction in asthma.
Gene Therapy for Head and Neck Cancer: Comparing the Tumor Suppressor Gene p53 and a Cell Cycle Regulator WAF1/CIP1 (p21) (1996)

Wild-type p53 adenovirus exhibits substantial in vitro and in vivo tumor suppressor activity in squamous cell carcinoma of the head and neck cell lines. This tumor suppression is not a function of the induced WAF1/CIP1 (p21) transcriptional product. Further studies are required to investigate the potential for induction of apoptosis by gene therapy.
PHOSPHORYLATION OF TAU BY GLYCOGEN SYNTHASE KINASE-3β IN VITRO PRODUCES SPECIES WITH SIMILAR ELECTROPHORETIC AND IMMUNOGENIC PROPERTIES TO PHF-TAU FROM AIZHEIMERS DISEASE BRAIN (1995)

Conference Article| February 01 1995 PHOSPHORYLATION OF TAU BY GLYCOGEN SYNTHASE KINASE-3β IN VITRO PRODUCES SPECIES WITH SIMILAR ELECTROPHORETIC AND IMMUNOGENIC PROPERTIES TO PHF-TAU FROM AIZHEIMERS DISEASE BRAIN S.F.C. Mulot; S.F.C. Mulot 1Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK Search for other works by this author on: This Site PubMed Google Scholar K. Hughes; K. Hughes 2Ontario Cancer Institute, Princess Margaret Hospital, 500 Sherboume Street, Toronto, Ontario M4X 1K9, Canada Search for other works by this author on: This Site PubMed Google Scholar J.R. Woodgett; J.R. Woodgett 2Ontario Cancer Institute, Princess Margaret Hospital, 500 Sherboume Street, Toronto, Ontario M4X 1K9, Canada Search for other works by this author on: This Site PubMed Google Scholar B.H. Anderton; B.H. Anderton 1Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK Search for other works by this author on: This Site PubMed Google Scholar D.P. Hanger D.P. Hanger 1Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (1): 45S. https://doi.org/10.1042/bst023045s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation S.F.C. Mulot, K. Hughes, J.R. Woodgett, B.H. Anderton, D.P. Hanger; PHOSPHORYLATION OF TAU BY GLYCOGEN SYNTHASE KINASE-3β IN VITRO PRODUCES SPECIES WITH SIMILAR ELECTROPHORETIC AND IMMUNOGENIC PROPERTIES TO PHF-TAU FROM AIZHEIMERS DISEASE BRAIN. Biochem Soc Trans 1 February 1995; 23 (1): 45S. doi: https://doi.org/10.1042/bst023045s 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 This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.
Immune Cell Recruitment and Cell-Based System for Cancer Therapy (2007)

Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy. Conventional studies of cancer immunotherapy have focused mainly on the search for an efficient means to prime/activate tumor-associated antigen-specific immunity. A systematic understanding of the molecular basis of the trafficking and biodistribution of immune cells, however, is important for the development of more efficacious cancer immunotherapies. It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues. Therefore, it is crucial to control the distribution of immune cells to optimize cancer immunotherapy. Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization. Here, we review the immune cell recruitment and cell-based systems that can potentially control the systemic pharmacokinetics of immune cells and, in particular, focus on cell migrating molecules, i.e., chemokines, and their receptors, and their use in cancer immunotherapy.
The Role of Free Radicals in Toxicity and Disease (1995)

Free radicals are defined as atoms or molecules that contain one or more unpaired electrons. The toxicity of many xenobiotics is associated with the metabolic activation of foreign compounds to form free radicals or with the production of reactive oxygen species as superoxide anion, hydroxyl radicals or hydrogen peroxide which are responsible for the tissue damaging effects as lipid peroxidation, and DNA and protein damage. Oxidative stress associated with production of reactive oxygen species is believed to be involved not only in the toxicity of xenobiotics but also in the pathophysiology of aging, and various age-related diseases, including cataracts, atherosclerosis, neoplastic diseases, diabetes, diabetic retinopathy, chronic inflammatory diseases of the gastrointestinal tract, aging of skin, diseases associated with cartilage, Alzheimer's disease, and other neurologic disorders. The cellular sources of free radicals and reactive oxygen species, the biological targets of free radicals, and clinical conditions which are associated with free radical production and tissue damage are reviewed. In addition, potential therapeutic approaches to the prevention of free radical damage are considered. Free radical-induced injury can explain many clinical conditions.
Cooling-Sensitive TRPM8 Is Thermostat of Skin Temperature against Cooling (2011)

We have shown that cutaneous cooling-sensitive receptors can work as thermostats of skin temperature against cooling. However, molecule of the thermostat is not known. Here, we studied whether cooling-sensitive TRPM8 channels act as thermostats. TRPM8 in HEK293 cells generated output (y) when temperature (T) was below threshold of 28.4°C. Output (y) is given by two equations: At T >28.4°C, y = 0; At T <28.4°C, y = -k(T - 28.4°C). These equations show that TRPM8 is directional comparator to elicits output (y) depending on negative value of thermal difference (ΔT = T - 28.4°C). If negative ΔT-dependent output of TRPM8 in the skin induces responses to warm the skin for minimizing ΔT recursively, TRPM8 acts as thermostats against cooling. With TRPM8-deficient mice, we explored whether TRPM8 induces responses to warm the skin against cooling. In behavioral regulation, when room temperature was 10°C, TRPM8 induced behavior to move to heated floor (35°C) for warming the sole skin. In autonomic regulation, TRPM8 induced activities of thermogenic brown adipose tissue (BAT) against cooling. When menthol was applied to the whole trunk skin at neutral room temperature (27°C), TRPM8 induced a rise in core temperature, which warmed the trunk skin slightly. In contrast, when room was cooled from 27 to 10°C, TRPM8 induced a small rise in core temperature, but skin temperature was severely reduced in both TRPM8-deficient and wild-type mice by a large heat leak to the surroundings. This shows that TRPM8-driven endothermic system is less effective for maintenance of skin temperature against cooling. In conclusion, we found that TRPM8 is molecule of thermostat of skin temperature against cooling.
Making gnutella-like P2P systems scalable (2003)

Napster pioneered the idea of peer-to-peer file sharing, and supported it with a centralized file search facility. Subsequent P2P systems like Gnutella adopted decentralized search algorithms. However, Gnutella's notoriously poor scaling led some to propose distributed hash table solutions to the wide-area file search problem. Contrary to that trend, we advocate retaining Gnutella's simplicity while proposing new mechanisms that greatly improve its scalability. Building upon prior research [1, 12, 22], we propose several modifications to Gnutella's design that dynamically adapt the overlay topology and the search algorithms in order to accommodate the natural heterogeneity present in most peer-to-peer systems. We test our design through simulations and the results show three to five orders of magnitude improvement in total system capacity. We also report on a prototype implementation and its deployment on a testbed.
Comparison of a Conserved Region in Fowlpox Virus and Vaccinia Virus Genomes and the Translocation of the Fowlpox Virus Thymidine Kinase Gene (1988)

The DNA sequence of a clustered set of genes which are conserved in orthopoxviruses has been determined for the avipoxvirus, fowlpox virus. The arrangement of the genes in fowlpox virus is nearly identical to that in vaccinia virus, and genes which are overlapping in vaccinia virus overlap in fowlpox virus. One major difference exists however, as the thymidine kinase (TK) gene is absent in fowlpox virus from the position it occupies within this cluster of genes in vaccinia virus. Instead, in fowlpox virus there is a 32 bp non-coding region present between the genes that flank the TK gene in vaccinia virus. The fowlpox virus TK gene has been cloned and sequenced. The sequences immediately flanking the TK gene show no homology to any previously reported poxvirus gene. These results are discussed in terms of genome stability in poxviruses and the use of the TK gene as a non-essential region for the introduction of foreign genes into poxviruses.