gebhart/patrepeval huggingface dataset:
A novel member of the integrin receptor family mediates Arg-Gly-Asp-stimulated neutrophil phagocytosis. (1989)

Human neutrophils (PMN) express a heterodimeric receptor that has ligand binding specificity for the Arg-Gly-Asp (RGD) sequence within many adhesive proteins. A monoclonal antibody, B6H12, which binds to this receptor, inhibits both RGD-mediated ligand binding and stimulation of IgG-mediated phagocytosis by fibronectin, fibrinogen, vitronectin, von Willebrand's factor, and collagen type IV. By several criteria this receptor is neither a known very late antigen, a known cytoadhesin (gp IIb/IIIa-vitronectin receptor), nor a member of the LFA-1, Mac-1, p150,95 group of integrin receptors. Ligand binding via this receptor is rapidly inactivated by products of the myeloperoxidase-hydrogen peroxide-halide system of PMN. We conclude that this receptor, for which we propose the name leukocyte response integrin, is a signal-transducing molecule on PMN which may have a significant early role in modulation of PMN function at inflammatory sites.
New mechanisms of signal transduction inhibitor action: receptor tyrosine kinase down-regulation and blockade of signal transactivation. (2003)

The explosion of signal transduction research over the last 10 years has provided a unique insight into the complexity of these intricate pathways. Whereas intermediates of multiple signaling pathways have been identified, understanding their function and, in particular, the interactions between them has become a daunting task. The increasing evidence that many of these pathways can cross-talk with each other via signal transactivation inevitably raises the question of how cells determine specificity in signaling. Despite the mind-numbing complexity of these pathways, progress has been made in developing highly specific and potent signal transduction inhibitors (STIs). STIs show promise in the treatment of cancer in preclinical studies and are currently in a number of clinical trials. Whereas many of these agents were "rationally designed," we barely understand their mechanisms of action. This review will highlight how recent studies using these STIs have elucidated novel mechanisms of STI action that may be used in the development of new therapeutic strategies for the treatment of cancer.
Purification of thioredoxin, thioredoxin reductase, and glutathione reductase by affinity chromatography. (1977)

A scheme is described for the large scale purification of thioredoxin, thioredoxin reductase, and glutathione reductase. The scheme is based on an initial separation of thioredoxin from the two reductases by affinity chromatography on agarose-bound N6-(6-aminohexyl)-adenosine 2',5'-bisphosphate (agarose-2',5'-ADP). The two reductases were then separated by hydrophobic chromatography and purified separately to homogeneity. Thioredoxin was purified to homogeneity by immunoadsorption to agarose containing immobilized goat anti-thioredoxin. Overall yields for thioredoxin, thioredoxin reductase, and glutathione reductase exceeded 80% in each case. Both reductases exhibit an absorption band at approximately 320 nm which appears due to a residual amount of tightly bound NADP. Presence of this absorption band has no apparent effect on the specific activity of either enzyme.
Response of Human Tongue Protrudor and Retractors to Hypoxia and Hypercapnia (1999)

It is well established that the genioglossus muscle (tongue protrudor) has a role in protecting or enhancing upper airway patency in individuals with obstructive sleep apnea. However, no investigation completed to date has addressed the role of the styloglossus and hyoglossus muscles (tongue retractors) in maintaining upper airway patency in humans. As a first step toward this goal, the present investigation was designed to examine the response of human tongue protrudor and retractor muscles during a breathhold maneuver and in steady-state hypoxic hypercapnia. The results showed that the protrudor and retractor muscles were coactivated under both conditions. Measurements of onset time of electromyographic activity during steady-state hypoxic hypercapnia revealed that phasic protrudor and retractor activity was initiated immediately before or during the early part of inspiration. We conclude that the tongue protrudor and retractor muscles are coactivated in response to hypoxia and hypercapnia, and that the tongue retractors may have a significant role in protecting upper airway patency during both apnea and hyperpnea.
Evidence for Regulation of Cholesterol and Fatty Acid Synthesis in Liver by Cyclic Adenosine 3′,5′-Monophosphate (1972)

Cyclic adenosine 3',5'-monophosphate at 5 X 1W5 M decreased the incorporation of [Z-*%]acetate into fatty acid (36 + 5%) in rat liver slices.Concentrations of cyclic adenosine 3',5'-monophosphate of 5 X 10da M and higher decreased cholesterol synthesis by more than 80%.The dibutyryl analog of the nucleotide produced a similar significant inhibition of fatty acid synthesis and cholesterol synthesis, but at concentrations up to loo-fold less.Metabolic evolution of COz was not significantly depressed at any concentration of either nucleotide.The data indicate that cyclic adenosine 3',5'-monophosphate may be involved in regulating acetyl-CoA incorporation into de nova fatty acid and cholesterol in a specific manner in mammalian liver.
Biomimetic syntheses of heptaketide metabolites: alternariol and a derivative of rubrofusarin (1978)

F. J. Leeper and J. Staunton, J. Chem. Soc., Chem. Commun., 1978, 406 DOI: 10.1039/C39780000406
Enzyme-Linked Immunosorbent Assay for the Diagnosis of Melioidosis: Better Than We Thought (2011)

We used Bayesian latent-class models to generate receiver operating characteristic curves and to revise the cutoff values for an enzyme-linked immunosorbent assay that has been developed previously for melioidosis. The new cutoff was unbiased towards misclassification caused by an imperfect gold standard and resulted in an increase in both sensitivity (from 66.4% to 80.2%) and specificity (82.1% and 95.0%).
In Vivo Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized 13C-Pyruvate (2009)

This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized (13)C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology.
Stimulation Characteristics, Complications, and Efficacy of Spinal Cord Stimulation Systems in Patients with Refractory Angina: A Prospective Feasibility Study (1994)

During a 1-year follow-up, the stimulation parameters did not change significantly in the 16 patients without lead dislocations. Our standardized method appears to be feasible for follow-up of SCS. Moreover, SCS seems to be an effective adjuvant therapy for intractable angina, despite a relatively frequent dislocation of the electrode.
Ultrastructure of compatible and incompatible interactions of soybean roots infected with the plant pathogenic oomycete Phytophthora sojae (1997)

Compatible and incompatible interactions of two soybean isolines containing either Rps1a or Rps1b resistance genes with races 2 and 8 of Phytophthora sojae were examined by light and electron microscopy. Phytophthora sojae race 2 is virulent on Rps1b plants and avirulent on Rps1a plants. Race 8 shows the reverse reaction; it is avirulent on Rps1b plants, but virulent on Rps1a plants. All combinations of races and cultivars were examined at times ranging from 30 min to 20 h postinoculation. Zoospore encystment, germination, and infection occurred within 30 min in all interactions. No evidence of appressorium formation was found. Wall appositions in epidermal cells adjacent to hyphae were very frequent by 30 min postinoculation. Differences between compatible and incompatible interactions became evident as early as 4 h postinoculation. The major difference appeared to relate to timing of host responses, which lead to two different types of relationships. In compatible interactions, P. sojae exhibited a short biotrophic phase with the establishment of many haustoria without triggering visible plant responses in cortical cells until approximately 10 h postinoculation. By 15 h postinoculation, almost the entire root was necrotic, wall appositions were abundant, and vascular tissue was colonized. The incompatible interaction was characterized by a nearly complete absence of haustoria, rapid host cell necrosis, and formation of many wall appositions by 4 h postinoculation. The pathogen rarely penetrated beyond the endodermis of the resistant host and colonization of vascular tissue was rare. Overall there were clear ultrastructural differences between compatible and incompatible interactions of soybean with P. sojae. These data support a strong correlation of resistance with host cell death, formation of wall appositions, and absence of root stele colonization. Key words: Phytophthora sojae, Glycine max, host–pathogen interaction, ultrastructure.
Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors. (1996)

Multidrug resistance (MDR) to anticancer drugs is a major cause of treatment failure in cancer. The lung resistance protein LRP is a newly described protein related to MDR in several in vitro models. LRP has been shown to be a strong predictor of poor response to chemotherapy and prognosis in acute myeloid leukemia and in ovarian carcinoma patients. Recently, based on a 57% and 88% amino acid identity with major vault proteins from Dictyostelium discoideum and Rattus norvegicus, respectively, we identified LRP as the human major vault protein, the main component of highly conserved cellular organelles named vaults. We have studied the immunohistochemical expression of LRP in freshly frozen normal human tissues and 174 cancer specimens of 28 tumor types. LRP was broadly distributed in normal and malignant cells, but distinct patterns of expression were noticed. High LRP expression was seen in bronchus, digestive tract, renal proximal tubules, keratinocytes, macrophages, and adrenal cortex whereas varying ing levels were observed in other organs. LRP was detected in all tumor types examined, but its frequency varied, fairly reflecting the chemosensitivity of different cancers. For example, low rates of LRP positivity were seen in testicular cancer, neuroblastoma, and acute myeloid leukemia; intermediate in ovarian cancer; and high in colon, renal, and pancreatic carcinomas. The wide occurrence of LRP in normal and transformed cells in humans, its similar distribution to that of vaults in other species, as well as the high level of conservation among eukaryotic cells of both the amino acid sequence of the major vault protein and the composition and structure of vaults, suggest that vault function is important to eukaryotic cells.
Cross-document summarization by concept classification (2002)

In this paper we describe a Cross Document Summarizer XDoX designed specifically to summarize large document sets (50-500 documents and more). Such sets of documents are typically obtained from routing or filtering systems run against a continuous stream of data, such as a newswire. XDoX works by identifying the most salient themes within the set (at the granularity level that is regulated by the user) and composing an extraction summary, which reflects these main themes. In the current version, XDoX is not optimized to produce a summary based on a few unrelated documents; indeed, such summaries are best obtained simply by concatenating summaries of individual documents. We show examples of summaries obtained in our tests as well as from our participation in the first Document Understanding Conference (DUC).
Targeting Axl and Mer Kinases in Cancer (2011)

Receptor tyrosine kinases (RTK) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play an important role in signal transduction in both normal and malignant cells. The mammalian TAM RTK family includes 3 closely related members: Tyro-3, Axl, and Mer. Overexpression or ectopic expression of the TAM receptors has been detected in a wide array of human cancers. Growth arrest-specific gene 6 has been identified as the major ligand for these TAM RTKs, and its binding to the receptors has been shown to promote proliferation and survival of cancer cells in vitro. Abnormal expression and activation of Axl or Mer can provide a survival advantage for certain cancer cells. Inhibition of Axl and Mer may enhance the sensitivity of cancer cells to cytotoxic agents and would potentially be a therapeutic strategy to target cancer cells. This review elucidates the role of Axl and Mer in normal cellular function and their role in oncogenesis. In addition, we review the potential to inhibit these RTKs for the development of therapeutic targets in treatment of cancer.
Fat-induced satiety factor oleoylethanolamide enhances memory consolidation (2009)

The ability to remember contexts associated with aversive and rewarding experiences provides a clear adaptive advantage to animals foraging in the wild. The present experiments investigated whether hormonal signals released during feeding might enhance memory of recently experienced contextual information. Oleoylethanolamide (OEA) is an endogenous lipid mediator that is released when dietary fat enters the small intestine. OEA mediates fat-induced satiety by engaging type-alpha peroxisome proliferator-activated receptors (PPAR-alpha) in the gut and recruiting local afferents of the vagus nerve. Here we show that post-training administration of OEA in rats improves retention in the inhibitory avoidance and Morris water maze tasks. These effects are blocked by infusions of lidocaine into the nucleus tractus solitarii (NTS) and by propranolol infused into the basolateral complex of the amygdala (BLA). These findings suggest that the memory-enhancing signal generated by OEA activates the brain via afferent autonomic fibers and stimulates noradrenergic transmission in the BLA. The actions of OEA are mimicked by PPAR-alpha agonists and abolished in mutant mice lacking PPAR-alpha. The results indicate that OEA, acting as a PPAR-alpha agonist, facilitates memory consolidation through noradrenergic activation of the BLA, a mechanism that is also critically involved in memory enhancement induced by emotional arousal.
Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. (1993)

Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major determinant of the thymic disease specificity of Moloney virus genetically maps to the conserved viral core motif in the Moloney virus enhancer. Point mutations introduced into the core site significantly shifted the disease specificity of the Moloney virus from thymic leukemia to erythroid leukemia (N.A. Speck, B. Renjifo, E. Golemis, T.N. Fredrickson, J.W. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We previously reported the purification of core-binding factors (CBF) from calf thymus nuclei (S. Wang and N.A. Speck, Mol. Cell. Biol. 12:89-102, 1992). CBF binds to core sites in murine leukemia virus and T-cell receptor enhancers. Affinity-purified CBF contains multiple polypeptides. In this study, we sequenced five tryptic peptides from two of the bovine CBF proteins and isolated three cDNA clones from a mouse thymus cDNA library encoding three of the tryptic peptides from the bovine proteins. The cDNA clones, which we call CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6, encode three highly related but distinct proteins with deduced molecular sizes of 22.0, 21.5, and 17.6 kDa that appear to be translated from multiply spliced mRNAs transcribed from the same gene. CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6 do not by themselves bind the core site. However, CBF beta p22.0 and CBF beta p21.5 form a complex with DNA-binding CBF alpha subunits and as a result decrease the rate of dissociation of the CBF protein-DNA complex. Association of the CBF beta subunits does not extend the phosphate contacts in the binding site. We propose that CBF beta is a non-DNA-binding subunit of CBF and does not contact DNA directly.
Lexical modeling in a speaker independent speech understanding system (1993)

Over the past 40 years, significant progress has been made in the fields of speech recognition and speech understanding. Current state-of-the-art speech recognition systems are capable of achieving word-level accuracies of 90% to 95% on continuous speech recognition tasks using 5000 words. Even larger systems, capable of recognizing 20,000 words are just now being developed. Speech understanding systems have recently been developed that perform fairly well within a restricted domain. While the size and performance of modern speech recognition and understanding systems are impressive, it is evident to anyone who has used these systems that the technology is primitive compared to our own human ability to understand speech. Some of the difficulties hampering progress in the fields of speech recognition and understanding stem from the many sources of variation that occur during human communication. One of the sources of variation that occurs in human communication is the different ways t...
Respiratory Infection of Mice with Vaccinia Virus (1967)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
The murine N-ras gene is not essential for growth and development. (1995)

The mammalian ras gene family encodes key cell-signaling, cell growth-related proteins that have been highly conserved in species from yeast to man. Specific point mutations in the ras genes are associated with various mammalian tumors. To understand the developmental role of the N-ras protooncogene in the mouse, we have disrupted its gene function by homologous recombination in embryonic stem cells. Mice derived from these cells that are homozygous for the N-ras mutation do not produce any detectable N-Ras protein and are morphologically and histologically indistinguishable from their heterozygous and wild-type siblings. Since N-ras is expressed at high levels in hematopoietic cells, we examined different populations of cells in peripheral blood and found no differences between mutant and normal animals. Our results show that N-ras gene function is dispensable for normal mouse development, growth, and fertility.
New procedure for DNA transfection with polycation and dimethyl sulfoxide. (1984)

A new procedure for DNA transfection has been developed in a system of chicken embryo fibroblast cells and cloned Rous sarcoma virus DNA by using a polycation reagent as a mediator to adsorb DNA to the cell surface and dimethyl sulfoxide as an agent to facilitate the uptake of adsorbed DNA by the cells. In this new, simple, and convenient polycation-dimethyl sulfoxide transfection, which requires no carrier DNA even with small amounts of DNA, the number of transformed cell foci induced by Rous sarcoma virus DNA was proportional to the dose of the transfecting DNA, and chicken embryo fibroblast cells were successfully transformed by v-src-containing subgenomic DNA as well.
Resiliency and Holistic Inhalant Abuse Treatment (2005)

In Canada, a major and innovative national response to inhalant abuse among First Nations youth has been the establishment of residential treatment centres through the federally funded National Native Youth Solvent Addiction program (NNYSA). This paper focuses on the role of a holistic conception of resiliency in inhalant abuse treatment in the NNYSA program. A blending of policy and practice issues and their contribution to the health status of First Nations youth inhalant abusers guide the paper’s discussion of resiliency and its fundamental role in NNYSA’s traditional Native teachings program. A holistic conception of resiliency is viewed as a key contributor to the program’s achievements to date. The focus on resiliency has been identified in assisting youth in uncovering their inner spirit and strengthening their spirit by drawing on available community resources. Data and case illustrations from two NNYSA treatment centres–White Buffalo Youth Inhalant Treatment Centre (Prince Albert, Sask.) and Nimkee NupiGawagan Healing Centre (Muncey, Ont.)–are presented. The paper also offers NNYSA policy solutions that have been guided by a holistic concept of resiliency and account for the intersecting roles of culture, spirituality, and community in creating and maintaining the health of First Nations youth solvent abusers. The paper concludes with suggestions for future research.
The Potential Role of mTOR Inhibitors in Non-Small Cell Lung Cancer (2008)

The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, which plays a critical role in regulating basic cellular functions including cellular growth and proliferation. Currently, the mTOR inhibitor rapamycin and its analogues (CCI-779, RAD001, AP23573), which induce cell-cycle arrest in the G(1) phase, are being evaluated in cancer clinical trials. The mTOR inhibitors appear to be well tolerated, with skin reactions, stomatitis, myelosuppression, and metabolic abnormalities the most common toxicities seen. These adverse events are transient and reversible with interruption of dosing. Several pieces of evidence suggest a certain antitumor activity, including tumor regressions and prolonged stable disease, which has been reported among patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). These promising preliminary clinical data have stimulated further research in this setting. Here, we review the basic structure of the pathway together with current results and future developments of mTOR inhibitors in the treatment of NSCLC patients.