gebhart/patrepeval huggingface dataset:
Similarity searching on CAS Registry substances. 1. Global molecular property and generic atom triangle geometric searching (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimilarity searching on CAS Registry substances. 1. Global molecular property and generic atom triangle geometric searchingWilliam Fisanick, Kevin P. Cross, and Andrew Rusinko IIICite this: J. Chem. Inf. Comput. Sci. 1992, 32, 6, 664–674Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://doi.org/10.1021/ci00010a013Request reuse permissionsArticle Views112Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-Alerts
Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein (2009)

Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.
Photoradiation of rabbit ocular malignant melanoma sensitized with hematoporphyrin derivative (1984)

Photoradiation therapy (PRT) against the Greene-Harvey amelanotic malignant melanoma on the rabbit iris was effectively used to cause tumor regression. A dose of 2.5 mg/kg of hematoporphyrin derivative (HPD) given intravenously, followed by photoradiation at a wavelength of 632 nm and a power density as low as 71 mW/cm2 for 24 minutes (102 J/cm2) was found to be lethal for tumors 4 mm in diameter with an acceptable level of reversible toxicity to the surrounding tissues. This was best accomplished with a dye laser as the source of light because of its very narrow expanding cone of light, as emitted from a fiber optic. A 1000 Watt xenon arc lamp was also effective but not as efficient. Because of this tumor's exceptionally rapid growth rate, it was necessary to compromise one important variable - the 3 to 4 day period between injection of HPD and photoradiation to allow for HPD depletion from normal tissues. Thus, the best tumor death responses were achieved when the light was given 1 to 16 hours after administering HPD. It is surmised that with this rapidly growing tumor, new cell progeny possess insufficient concentrations of HPD to be killed by the radiant energy. At such a short delay period, toxicity to normal tissues was observed mainly as conjunctivitis and conjunctival chemosis. A dose level of HPD at 5 mg/kg was very close to the threshold where minor increases in light intensity would cause strong inflammatory reactions. Higher doses, at 7.5 and 10 mg/kg were excessive. A dose of 23 mg/kg accompanied by mild light energy exposures, even after 30 days, caused massive damage to normal tissues.
Activation of microglia reveals a non-proteolytic cytokine function for tissue plasminogen activator in the central nervous system (1999)

Tissue plasminogen activator mediates excitotoxin-induced neurodegeneration and microglial activation in the mouse hippocampus. Here we show that tissue plasminogen activator (tPA) acts in a protease-independent manner to modulate the activation of microglia, the cells of the central nervous system with macrophage properties. Cultured microglia from tPA-deficient mice can phagocytose as efficiently as wild-type microglia. However, tPA-deficient microglia in mixed cortical cultures exhibit attenuated activation in response to lipopolysaccharide, as judged by morphological changes, increased expression of the activation marker F4/80 and the release of the pro-inflammatory cytokine tumor necrosis factor-(&agr;). When tPA is added to tPA deficient cortical cultures prior to endotoxin stimulation, microglial activation is restored to levels comparable to that observed in wild-type cells. Proteolytically-inactive tPA can also restore activation of tPA-deficient microglia in culture and in vivo. However, this inactive enzyme does not restore susceptibility of tPA-deficient hippocampal neurons to excitotoxin-mediated cell death. These results dissociate two different functions of tPA: inactive enzyme can mediate microglial activation, whereas proteolytically-competent protein also promotes neuronal degeneration. Thus tPA is identified as a new cytokine in the central nervous system.
Abstract 1052: In vitro mechanism of action of AZD5363, a novel AKT inhibitor, in breast and prostate cancer cell lines (2011)

Abstract AKT (protein kinase B) is a key regulator of the phosphoinositide-3-kinase signaling pathway and plays a key role in mediating signals for cell growth, survival and differentiation. This pathway is among the most commonly de-regulated pathways in human cancer and represents a key target for therapeutic intervention. Here, we describe the in-vitro mechanism of action of AZD5363, a potent small molecule inhibitor of AKT1, AKT2 and AKT3. We show that treatment of breast and prostate cancer cell lines with AZD5363 leads to inhibition of phosphorylation of a number of AKT substrates including PRAS40, GSK-3β and the downstream marker, P70S6K. In the BT474c cell line, &amp;gt;90% inhibition of phosphorylation of PRAS40 was observed at 1uM and this effect was sustained for 24 hours. Inhibition of phosphorylation of 4E-BP1, a key regulator of protein translation, was also observed when treating cells with AZD5363. We demonstrate that inhibition of phosphorylation of 4EBP1 (Thr37/46) is associated with an induction of 4E-BP1 binding to the eIF4E-mRNA CAP complex within 1 hour of dosing with AZD5363, consistent with inhibition of CAP-dependent protein translation. Analysis of phenotypic endpoints indicates that AZD5363 is a potent inhibitor of proliferation in the majority of breast and prostate cell lines studied. In addition, in a subset of cell lines, treatment with AZD5363 was shown to induce a cytotoxic phenotype measured by a Sytox Green endpoint. In the BT474c cell line, 1uM AZD5363 inhibited phosphorylation of 4E-BP1 by 50% at 24 hours and induced 11% apoptosis at 72 hours. This data demonstrates that AZD5363 has profound effects on downstream effectors of the PI3K/AKT pathway consistent with that of an Akt inhibitor which results in an anti-proliferative, and in some cases cytotoxic, profile in breast and prostate cell lines. AZD5363 is currently in Phase I clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1052. doi:10.1158/1538-7445.AM2011-1052
Effects of Combined Antigrowth Factor Receptor Treatment on In Vitro Growth of Multiple Myeloma (1994)

Anti-receptor antibodies have distinct patterns of myeloma cell growth inhibition and inhibit in vitro growth of factor-dependent myeloma cells. Combinations of anti-growth factor receptor antibodies also increase toxicity for IL-6-dependent myeloma colony-forming units.
Expression of folate receptor type alpha in relation to cell type, malignancy, and differentiation in ovary, uterus, and cervix. (1999)

The folate receptor (FR) type alpha is known to be frequently overexpressed in ovarian cancer and is the target for a number of novel experimental cancer therapies. The relative levels of FR expression among specific cell types and its relationship to malignant transformation have not been adequately established because of several inherent limitations of the immunocytochemical approaches used previously. We used a quantitative in situ hybridization method to examine the expression of the mRNAs for the known isoforms of FR in paraffin-embedded tissue sections of multiple samples of the various subtypes of ovarian, uterine, and cervical cancers. Benign lesions, as well as the various normal cell types in the ovary, the uterus, and the cervix, were examined similarly. FR mRNA levels were quantitated relative to the transcript levels for beta-actin using NIH Image 1.57 computer software. The results show that the ovary, the uterus, and the cervix present different patterns of FR regulation in differentiation and in malignancy. In the ovary, benign differentiation of the germinal epithelium into mucinous or serous tumors or malignant transformation into mucinous tumors is associated with down-regulation of FR-alpha, whereas FR-alpha expression is retained in malignant lesions of serous and endometrioid differentiation. In contrast, malignant transformation of the glandular epithelial cells of the uterine endometrium is associated with de novo expression of FR-alpha. Heterogeneity in FR expression within malignant ovarian and uterine tumors is related to differentiation. In contrast to the uterus, malignant transformation of glandular epithelial cells in the cervix may frequently result in down-regulation of FR-alpha. These results shed new light for the identification of malignancies suitable for FR-mediated therapies and for prognostic/diagnostic applications of FR. They also provide a phenomenological basis for molecular studies of FR regulation in malignant cells.
Nonalcoholic fatty liver disease (2008)

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximately 75-92% and in the pediatric population at approximately 13-14%. The progressive form of NAFLD, nonalcoholic steatohepatitis, is estimated at approximately 3-5%, with approximately 3-5% of these having progressed to cirrhosis. Thus, the numbers of individuals at risk for end-stage liver disease and development of primary liver cancer is large. NAFLD is an independent risk factor for cardiovascular disease, leads to increased all-cause mortality, and to increased liver-related mortality. This review focuses on recent advances in our understanding of the NAFLD disease spectrum, including etiology, diagnosis, treatment, and genetic and environmental risk factors and suggests future directions for research in this important area.
Suzuki−Miyaura Cross-Coupling of Benzylic Phosphates with Arylboronic Acids (2005)

[reaction: see text] Suzuki-Miyaura cross-coupling of benzylic phosphates with arylboronic acids was investigated. Optimum conditions employed the simple catalytic system of palladium(II) acetate (1 mol %) and triphenylphosphine (4 mol %) with either potassium phosphate or potassium carbonate as the base and toluene as the solvent at 90 degrees C. Using the developed conditions, a series of structurally diverse diarylmethanes were prepared.
Autologous bone marrow cell therapy for peripheral arterial disease (2012)

Inadequate blood supply to tissues caused by obstruction of arterioles and/or capillaries results in ischemic injuries - these injuries can range from mild (eg, leg ischemia) to severe conditions (eg, myocardial infarction, stroke). Surgical and/or endovascular procedures provide cutting-edge treatment for patients with vascular disorders; however, a high percentage of patients are currently not treatable, owing to high operative risk or unfavorable vascular involvement. Therapeutic angiogenesis has recently emerged as a promising new therapy, promoting the formation of new blood vessels by the introduction of bone marrow-derived stem and progenitor cells. These cells participate in the development of new blood vessels, the enlargement of existing blood vessels, and sprouting new capillaries from existing blood vessels, providing evidence of the therapeutic utility of these cells in ischemic tissues. In this review, the authors describe peripheral arterial disease, an ischemic condition affecting the lower extremities, summarizing different aspects of vascular regeneration and discussing which and how stem cells restore the blood flow. The authors also present an overview of encouraging results from early-phase clinical trials using stem cells to treat peripheral arterial disease. The authors believe that additional research initiatives should be undertaken to better identify the nature of stem cells and that an intensive cooperation between laboratory and clinical investigators is needed to optimize the design of cell therapy trials and to maximize their scientific rigor. Only this will allow the results of these investigations to develop best clinical practices. Additionally, although a number of stem cell therapies exist, many treatments are performed outside international and national regulations and many clinical trials have been not registered on databases such as ClinicalTrials.gov or EudraCT. Therefore, more rigorous clinical trials are required to confirm the first hopeful results and to address the challenging issues.
Endothelin Receptor B Inhibition Triggers Apoptosis and Enhances Angiogenesis in Melanomas (2004)

Endothelin receptor B (ETRB or EDNRB) is overexpressed in most human melanomas and is proposed to provide a marker of melanoma progression. We have shown previously that inhibition of ETRB leads to increased human melanoma cell death in vitro and in vivo, resulting in shrinkage of tumors grown in immunocompromised mice. In the present work, we analyzed the effects of ETRB inhibition on 10 human melanoma cell lines derived from tumors at distinct stages of progression. Our observations suggest that the ETRB antagonist BQ788 induces apoptosis most effectively in metastatic melanoma cells. Microarray analysis shows that BQ788 treatment leads to a reduction in the expression of the survival factor BCL-2A1 and the DNA repair factor poly(ADP-ribose) polymerase 3 that is more pronounced in cells derived from metastatic than primary melanoma. Decreased cell viability was observed to correlate with reduction in ETRB expression, and reduction in ETRB protein levels by small interfering RNA led to an increase in cell death. Interestingly, reduction of ETRB expression by BQ788 was accompanied by a strong induction of VEGF expression and repression of the angiogenic suppressor gravin. These changes in gene expression correlated with increased angiogenesis in tumors injected with ETRB antagonist in vivo. Taken together, our observations suggest that ETRB may provide a potential therapeutic target in high-grade melanomas and identify candidate pathways that may be implicated in the regulation of cell survival and tumor progression associated with ETRB signaling.
Experimental and theoretical study of dielectrophoretic particle trapping in arrays of insulating structures: Effect of particle size and shape (2014)

Insulator-based dielectrophoresis (iDEP) employs insulating structures embedded in a microchannel to produce electric field gradients. This contribution presents a detailed analysis of the regions within an iDEP system where particles are likely to be retained due to dielectrophoretic trapping in a microchannel with an array of cylindrical insulating structures. The effects of particle size and shape on dielectrophoretic trapping were analyzed by employing 1 and 2 μm polystyrene particles and Escherichia coli cells. This research aims to study the mechanism behind dielectrophoretic trapping and develop a deeper understanding of iDEP systems. Mathematical modeling with COMSOL Multiphysics was employed to assess electrokinetic and dielectrophoretic particle velocities. Experiments were carried out to determine the location of dielectrophoretic barriers that block particle motion within an iDEP microchannel; this supported the estimation of a correction factor to match experiments and simulations. Particle velocities were predicted with the model, demonstrating how the different forces acting on the particles are in equilibrium when particle trapping occurs. The results showed that particle size and shape have a significant effect on the magnitude, location, and shape of the regions of dielectrophoretic trapping of particles, which are defined by DEP isovelocity lines and EK isovelocity lines.
1993 Syntex Award Lecture Photomedicine and photodynamic therapy (1994)

Photodynamic therapy (PDT) involves the treatment of diseased tissue and cells using a photosensitizer and visible light. Such photomedical treatments have been known since the time of the ancient Egyptians but it was only just this year that this therapeutic modality was made available to modern medicine with the approval, in Canada, of Photofrin® for the treatment of bladder cancer. This paper reviews PDT with an emphasis on drug development, particulary for the second generation drugs, especially BPDMA (benzoporphyrin derivative-mono acid), which is now in human clinical trials.
Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine (2019)

An improved understanding of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein structure and the consequences of <i>CFTR</i> gene mutations have allowed the development of novel therapies targeting specific defects underlying CF. Some strategies are mutation specific and have already reached clinical development; some strategies include a read-through of the specific premature termination codons (read-through therapies, nonsense mediated decay pathway inhibitors for Class I mutations); correction of CFTR folding and trafficking to the apical plasma membrane (correctors for Class II mutations); and an increase in the function of CFTR channel (potentiators therapy for Class III mutations and any mutant with a residual function located at the membrane). Other therapies that are in preclinical development are not mutation specific and include gene therapy to edit the genome and stem cell therapy to repair the airway tissue. These strategies that are directed at the basic CF defects are now revolutionizing the treatment for patients and should positively impact their survival rates.
Mithramycin forms a stable dimeric complex by chelating with Fe(II): DNA-interacting characteristics, cellular permeation and cytotoxicity (2005)

Mith (mithramycin) forms a 2:1 stoichiometry drug-metal complex through the chelation with Fe(II) ion as studied using circular dichroism spectroscopy. The binding affinity between Mith and Fe(II) is much greater than other divalent metal ions, including Mg(II), Zn(II), Co(II), Ni(II) and Mn(II). The [(Mith)2-Fe(II)] complex binds to DNA and induces a conformational change of DNA. Kinetic analysis of surface plasmon resonance studies revealed that the [(Mith)2-Fe(II)] complex binds to DNA duplex with higher affinity compared with the [(Mith)2-Mg(II)] complex. A molecular model of the Mith-DNA-Metal(II) complex is presented. DNA-break assay showed that the [(Mith)2-Fe(II)] complex was capable of promoting the one-strand cleavage of plasmid DNA in the presence of hydrogen peroxide. Intracellular Fe(II) assays and fluorescence microscopy studies using K562 indicated that this dimer complex maintains its structural integrity and permeates into the inside of K562 cells, respectively. The [(Mith)2-Fe(II)] complex exhibited higher cytotoxicity than the drug alone in some cancer cell lines, probably related to its higher DNA-binding and cleavage activity. Evidences obtained in this study suggest that the biological effects caused by the [(Mith)2-Fe(II)] complex may be further explored in the future.
The Natural Distribution of Tritium (1954)

The abundance of cosmic-ray-produced tritium has been measured in a variety of natural waters in the Mississippi Valley, the Chicago area, and in a few places elsewhere in the northern hemisphere. Contents ranging between 0.5 and 67 tritium atoms per ${10}^{18}$ hydrogen atoms have been found. These correspond to an average cosmic-ray production rate of about 0.12 tritium atoms per ${\mathrm{cm}}^{2}$ per second if the total rate of transfer of tritium into the oceans by oceanic rain and snow and by rivers carrying continental water is taken as being equal to the total production rate. This is equivalent to assuming short land storage time in terms of eighteen years---the tritium average life. This production rate corresponds to an inventory of about 1800 g, with only about one percent of this in the atmosphere.The tritium contents of vintage wines appear to agree with the time elapsed since bottling, indicating the tritium abundances over the last eighteen years to have been essentially equal to the present ones. Some of the possible applications of natural tritium to problems of hydrology and meteorology are discussed. The present production rate for tritium corresponds to an ${\mathrm{He}}^{3}$ escape rate from the earth of about 5\ifmmode\times\else\texttimes\fi{}${10}^{7}$ years or less.
Identification of the TS2/18-recognized epitope on the CD2 molecule as a target for suppression of T cell cytokine synthesis. (1995)

CD2 mAb can inhibit T cell activation, but the mechanisms involved are still unclear. In this study, we identify the mAb TS2/18, previously reported to bind to an epitope on the distal domain of the CD2 molecule at amino acids 87-99 (1), as a particularly potent inhibitor of T cell cytokine synthesis. Although TS2/18 is comitogenic with the CD2R mAb VIT13, this mAb combination does not induce the secretion of substantial amounts of cytokines. When added to T cells stimulated with the CD2 mAb pair OKT11-VIT13, TS2/18 efficiently blocks the induction of cytokine synthesis induced by that CD2 mAb pair, although it does not interfere with the binding of OKT11. In addition, TS2/18 inhibits the increase in protein tyrosine phosphorylation and the accumulation of phosphatidic acid induced by either OKT11-VIT13 or a cross-linked CD3 mAb. Finally, TS2/18 disrupts CD2 clusters induced by the CD2 mAb pair OKT11-VIT13. We conclude that TS2/18 blocks T cell cytokine synthesis by interfering with early signal transduction, possibly by impairing the formation of signal-transducing molecule complexes on the T cell surface. Together, these data identify the CD2 epitope recognized by the mAb TS2/18 as a candidate epitope for T cell-specific immunosuppressive ligands.