gebhart/patrepeval huggingface dataset:
Development of Molecular Agents for IGF Receptor Targeting (2003)

The type 1 insulin-like growth factor receptor (IGF1R) is a promising anticancer treatment target, being frequently overexpressed by tumours, and mediating proliferation, motility and apoptosis protection. Design of specific kinase inhibitors is problematic because of homology between the IGF1R and insulin receptor. This obstacle can be circumvented using sequence-specific molecular agents including antisense, triplex and ribozymes. Recent studies indicate that profound sequence-specific IGF1R gene silencing can be induced by small interfering RNAs that mediate RNA interference in mammalian cells. IGF1R downregulation blocks tumour growth and metastasis, and enhances sensitivity to cytotoxic drugs and irradiation. In murine melanoma cells, radiosensitisation is associated with impaired activation of Atm, which is required for initiation of cell cycle checkpoints and DNA repair pathways after double-strand DNA breaks. Furthermore, tumour cells killed in vivo following IGF1R downregulation can provoke an immune response, protecting against tumour rechallenge. After years of studying the role of the IGF system in tumour biology, novel agents for IGF1R targeting will soon be available for clinical testing. This review summarises the development of molecular agents, and considers factors that will influence clinical activity, including the requirement of established tumours for IGF signalling, and the efficacy and toxicity of IGF1R inhibitors.
Radical detection in a methane plasma (2003)

We present a method for detecting and quantifying the concentration of free radicals produced in a low temperature methane process plasma employing quadrupole mass spectrometry and Bayesian analysis. The latter includes a model comparison to determine species expected in the plasma and a parameter estimation of their concentrations and cracking coefficients. We find that the neutral mass spectra are best explained by incorporating the neutral molecules H2, CH4, C2H2, C2H4, and C2H6 as well as the radicals H, CH3, and C2H5 into the model.
Growth inhibition of human tumor cells in soft-agar cultures by treatment with low levels of adenosine 5'-triphosphate. (1983)

Treatment of a variety of human tumor cells in monolayer cultures with low levels (40 to 80 microM) of adenosine 5'-diphosphate (ADP) or adenosine 5'-triphosphate (ATP) was recently shown to produce arrest of cellular growth in the S phase of the cell cycle (E. Rapaport, J. Cell. Physiol., 114: 279-283, 1983). We now demonstrate that exposure of two well-characterized colonic adenocarcinoma (HT-29 and SW-620) and two pancreatic adenocarcinoma (CAPAN-1 and PANC-1) cell lines in soft-agar cultures to exogenously supplied 5 to 20 microM ATP results in substantial inhibition of cellular growth. Exposure of the cells to 5 to 20 microM ADP produces slightly smaller growth-inhibitory effects, while 20 microM adenosine 5'-monophosphate or adenosine have marginal effects on cellular proliferation in these systems. Successful demonstration of these effects requires the use of heat-inactivated fetal bovine serum, since normal fetal bovine serum possesses enzymatic activities which catalyze the rapid degradation of adenine nucleotides. Tumor cell growth was assayed by the well-established colony formation assay as well as by [3H]thymidine incorporation into acid-insoluble material. [3H]Thymidine incorporation is performed 4 to 14 days after plating and correlates well with results obtained by colony formation assays. Due to the ectoenzymatic activities of the cells which include adenosinetriphosphatase and adenosinediphosphatase catalyzing the dephosphorylation of ATP and ADP, the effective levels of ATP that inhibit the growth of human tumor cells in this system, which is widely claimed to predict the in vivo response of a tumor, are lower than the 5 to 20 microM which are exogenously supplied. The two previously characterized, well-differentiated pancreatic and colonic tumor cell lines (CAPAN-1 and HT-29) were shown to exhibit higher chemosensitivity towards treatment with ATP and ADP than did the lesser-differentiated pancreatic and colonic tumor cell lines (PANC-1 and SW-620).
Cell type-specific glycoforms of Fc gamma RIIIa (CD16): differential ligand binding (1997)

Fc gamma RIIIa, considered an intermediate affinity receptor, can variably bind monomeric IgG and appears to have a higher affinity for IgG than the lower affinity Fc gamma Rs, Fc gamma RII and Fc gamma RIIIb. We explored this property for both NK cell and monocyte Fc gamma RIIIa and found higher affinity ligand binding by Fc gamma RIIIa expressed on NK cells compared with Fc gamma RIIIa on monocytes. In normal whole blood or plasma (containing 8-11 mg/ml IgG), NK cell Fc gamma RIIIa was fully blocked, but in monocytes Fc gamma RIIIa showed approximately 60% blockade of the binding of mAb 3G8, which binds in or near the ligand binding site. The ligand binding site of NK cell Fc gamma RIIIa was blocked with as little as 2 mg/ml of human IgG, while monocyte Fc gamma RIIIa was only partially (30%) blocked by 2 mg/ml of human IgG. In contrast, plasma containing approximately 26 mg/ml of IgG (obtained from patients receiving therapeutic gamma-globulin) showed complete saturation of monocyte Fc gamma RIIIa with blockade of mAb 3G8 binding. These binding differences are not due to allelic polymorphisms or primary sequence differences between donors. Although NK cell and monocyte Fc gamma RIIIa have identical protein cores, they each undergo differential cell type-specific glycosylation. NK cell Fc gamma RIIIa is glycosylated with high mannose- and complex-type oligosaccharides, while monocyte Fc gamma RIIIa has no high mannose-type oligosaccharides. These results indicate that natural glycoforms of Fc gamma RIIIa (cell type-specific glycosylation variants) bind ligand differently, conferring a lower affinity on monocyte/macrophage Fc gamma RIIIa, which makes the receptor ideal for initial immune complex capture and sensitive to moderate changes in serum IgG levels.
Autologous Designer Antigen-presenting Cells by Gene Modification of T Lymphocyte Blasts With IL-7 and IL-12 (2007)

An effective immune response to antigen requires professional antigen-presenting cell (APC), which not only present antigen, but also provide costimulation and cytokines (eg, IL-12) that drive T cell differentiation down the appropriate effector pathway (Tc1/TH1). For T cell-based immunotherapy protocols, the availability of large numbers of autologous professional APC is a major limitation because professional APC do not proliferate in vitro. T cells themselves can proliferate exponentially in vitro and have the ability to present antigen. They can also express costimulatory molecules after activation. Therefore, we hypothesized that if activated T cells were genetically modified to express proinflammatory cytokines required to polarize T cells toward a Tc1 response, they could fulfill the requirements for an abundant, autologous APC. To test this potential, T cells were activated by CD3/CD28 antibodies and pulsed with model HLA-A2+ peptides derived from CMVpp65, MAGE-3, and MART-1. Activated T-APC readily reactivated CD8 pp65 memory T cells from healthy CMV seropositive donors; however, the activation of MAGE-3 and MART-1-specific CD8 T cells required both IL-7 and IL-12, which could be provided either exogenously or by genetic modification of the T-APC. Responder T cells could be expanded to large numbers with subsequent stimulations using activated, peptide-pulsed T-APC and IL-2. Tumor antigen-specific T cell lines killed both peptide-pulsed target cells and tumor cell lines. Thus, T cells provide a platform for the generation of autologous APC that can be customized to express both antigens and therapeutic molecules for the induction of antigen-specific T cell immunity.
Signal Transduction through Tyrosine-phosphorylated C-terminal Fragments of Amyloid Precursor Protein via an Enhanced Interaction with Shc/Grb2 Adaptor Proteins in Reactive Astrocytes of Alzheimer's Disease Brain (2002)

The proteolytic processing of amyloid precursor protein (APP) through the formation of membrane-bound C-terminal fragments (CTFs) and of soluble beta-amyloid peptides likely influences the development of Alzheimer's disease (AD). We show that in human brain a subset of CTFs are tyrosine-phosphorylated and form stable complexes with the adaptor protein ShcA. Grb2 is also part of these complexes, which are present in higher amounts in AD than in control brains. ShcA immunoreactivity is also greatly enhanced in patients with AD and occurs at reactive astrocytes surrounding cerebral vessels and amyloid plaques. A higher amount of phospho-ERK1,2, likely as result of the ShcA activation, is present in AD brains. In vitro experiments show that the ShcA-CTFs interaction is strictly confined to glial cells when treated with thrombin, which is a well known ShcA and ERK1,2 activator and a regulator of APP cleavage. In untreated cells ShcA does not interact with either APP or CTFs, although they are normally generated. Altogether these data suggest that CTFs are implicated in cell signaling via Shc transduction machinery, likely influencing MAPK activity and glial reaction in AD patients.
Reversible Inhibition of Calcineurin by the Polyphenolic Aldehyde Gossypol (2001)

The reversible inhibition of calcineurin (CaN), which is the only Ca(2+)/calmodulin-dependent protein Ser/Thr phosphatase, is thought to be a key functional event for most cyclosporin A (CsA)- and tacrolimus (FK506)-mediated biological effects. In addition to CaN inhibition, however, CsA and FK506 have multiple biochemical effects because of their action in a gain-of-function model that requires prior binding to immunophilic proteins. We screened a small molecule library for direct inhibitors of CaN using CaN-mediated dephosphorylation of (33)P-labeled 19-residue phosphopeptide substrate (RII phosphopeptide) as an assay and found the polyphenolic aldehyde gossypol to be a novel CaN inhibitor. Unlike CsA and FK506, gossypol does not require a matchmaker protein for reversible CaN inhibition with an IC(50) value of 15 microm. Gossypolone, a gossypol analog, showed improved inhibition of both RII phosphopeptide and p-nitrophenyl phosphate dephosphorylation with an IC(50) of 9 and 6 microm, respectively. In contrast, apogossypol hexaacetate was inactive. Gossypol acts noncompetitively, interfering with the binding site for the cyclophilin 18.CsA complex in CaN. In contrast to CsA and FK506, gossypol does not inactivate the peptidyl-prolyl-cis/trans-isomerase activity of immunophilins. Similar to CsA and FK506, T cell receptor signaling induced by phorbol 12-myristate 13-acetate/ionomycin is inhibited by gossypol in a dose-dependent manner, demonstrated by the inhibition of nuclear factor of activated T cell (NFAT) c1 translocation from the cytosol into the nucleus and suppression of NFAT-luciferase reporter gene activity.
HYDROLYSIS OF ALKYL ACETATES IN A PHOSPHATE-BUFFERED AQUEOUS MEDIUM (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHYDROLYSIS OF ALKYL ACETATES IN A PHOSPHATE-BUFFERED AQUEOUS MEDIUMJohn M. Holland and John G. MillerCite this: J. Phys. Chem. 1961, 65, 3, 463–466Publication Date (Print):March 1, 1961Publication History Published online1 May 2002Published inissue 1 March 1961https://pubs.acs.org/doi/10.1021/j100821a018https://doi.org/10.1021/j100821a018research-articleACS PublicationsRequest reuse permissionsArticle Views118Altmetric-Citations6LEARN 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 InRedditEmail Other access options Get e-Alerts
Laser-Enabled Advanced Packaging of Ultrathin Bare Dice in Flexible Substrates (2011)

Embedding ultrathin semiconductor dice in flexible substrates provides unique capabilities for product designers and makes products such as smart bank cards and radio-frequency identification banknotes possible. Most of the current work in this area is directed toward handling, embedding, and interconnecting the ultrathin chips. Relatively little attention is paid to another critical process step-placing the flexible and very fragile ultrathin die onto the flexible substrate reliably and in a cost-efficient manner, suitable for high throughput assembly. The presented laser-enabled technology for embedding ultrathin dice in a flexible substrate was developed at the Center for Nanoscale Science and Engineering, North Dakota State University, Fargo, ND, to address this problem. The technology has been successfully demonstrated and proven for the fabrication of an RFID tag.
Panitumumab: A Summary of Clinical Development in Colorectal Cancer and Future Directions (2012)

Panitumumab is a fully human, monoclonal antibody targeting the EGF receptor with proven clinical activity in KRAS wild-type metastatic colorectal carcinoma. Treatment with panitumumab has been shown to significantly improve response rate and progression-free survival in this subgroup of patients, with a manageable toxicity profile. Panitumumab's first worldwide indication was as a single agent in chemorefractory patients. Recently, the EMA approved its use as part of a chemotherapy regimen in first- and second-line settings, following the encouraging results of large randomized Phase III trials. In order to identify patients with higher chances of benefiting from the treatment, additional molecular aberrations in the EGF receptor signaling pathway are being investigated as predictive biomarkers. In this article we review 10 years of drug development, focusing on the clinical evidence for panitumumab's indication in metastatic colorectal cancer and future strategies of investigation.
Selective reactions using allylic metals (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective reactions using allylic metalsYoshinori. Yamamoto and Naoki. AsaoCite this: Chem. Rev. 1993, 93, 6, 2207–2293Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 September 1993https://pubs.acs.org/doi/10.1021/cr00022a010https://doi.org/10.1021/cr00022a010research-articleACS PublicationsRequest reuse permissionsArticle Views7595Altmetric-Citations1432LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Influence of ischemic zone size on nonischemic area function in the canine left ventricle (1987)

The relationship between ischemic zone size and nonischemic area function was examined in seven anesthetized dogs. Regional ventricular function was measured with sonomicrometers implanted in the midwall of the anterior apex, posterior base, and posterior apex of the left ventricle. Ventricular volume was varied to three levels, corresponding to left ventricular end-diastolic pressures of 7, 12, and 19 mmHg. A small, moderate, and large area of anterior wall ischemia was produced with sequential occlusions of the distal, mid, and proximal left anterior descending coronary artery, respectively. Each occlusion was maintained for 15-30 min; then ventricular volume was varied to three levels, chosen so that end-diastolic segment lengths in the nonischemic areas were matched to their control (preischemia) values. With acute ischemia, paradoxical lengthening developed in the ischemic zone during isovolumic systole. This was accompanied by an increase in isovolumic shortening in the nonischemic areas. The amount of nonischemic area isovolumic shortening increased with increasing ischemic zone size, suggesting that more nonischemic area shortening was expended in paradoxically stretching the ischemic zone. With moderate and large areas of ischemia, the amount of "wasted" isovolumic shortening by nonischemic areas was greater at low than at high ventricular volumes. It is concluded that the ischemic zone imposes a mechanical disadvantage on nonischemic areas in direct relation to ischemic zone size and is inversely related to the ventricular volume.
Comparative penetration of cefonicid and cefazolin into the atrial appendage and pericardial fluid of patients undergoing open-heart surgery (1984)

The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentrations of cefonicid in serum and the atrial appendage were at least twice those observed for cefazolin at a given time after a dose. The mean (+/- standard deviation) atrial appendage-serum ratio was 0.47 +/- 0.14 for cefonicid and 0.34 +/- 0.06 for cefazolin (P less than 0.005). Pericardial fluid concentrations of cefonicid were slightly lower than those observed in patients receiving cefazolin (P greater than 0.05). A single intravenous dose of cefonicid provides high and sustained concentrations in serum and cardiac tissue and thus may be useful in antibiotic prophylaxis of certain surgical procedures; however, further study of the efficacy of this agent in the prevention and treatment of infections associated with Staphylococcus spp. is needed.
Electron microscopy on high-coercive-force Co-Cr composite films (1970)

Electron microscopy was used to analyze the crystallographic and magnetic structures of high-coercive-force Co-Cr composite films. The chromium sublayer appears to give high coercive forces by causing the growth of cobalt in the hexagonal phase with a relatively narrow distribution of grain sizes. Magnetization reversal was examined by Lorentz microscopy of films with coercive fields up to <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H_{c} = 900</tex> Oe. It proceeds by nucleation and extension of magnetostatically coupled domains. The progressive limitation of these extensions as the coercive force increases illustrates the connection between the magnetostatic coupling, the coercive force, and the squareness of the hysteresis loop. Lorentz microscopy was also used to investigate a recorded transition between NRZ 1 and 0 states and showed a saw-toothed structure, characteristic of a magnetization in the plane of the film.
Broad-spectrum coronavirus antiviral drug discovery (2019)

The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic.
Organic Photovoltaics (2007)

Organic photovoltaics, the technology to convert sun light into electricity by employing thin films of organic semiconductors, has been the subject of active research over the past 20 years and has received increased interest in recent years by the industrial sector. This technology has the potential to spawn a new generation of low-cost, solar-powered products with thin and flexible form factors. Here, we introduce the energy and environmental science community to the basic concepts of organic photovoltaics and discuss some recent science and engineering results and future challenges.
Metastasis Research Protocols (2001)

Although ninety percent of fatal cancer cases involve the spread of a primary tumor, the formation of metastases is still a poorly understood, complex process and a significant problem in the treatment of cancer patients. In Metastasis Research Protocols, leading international investigators describe the key methods needed to investigate why and how metastasis occurs. Volume I of this two-volume set, Analysis of Cells and Tissues, presents a comprehensive collection of established and leading-edge techniques for analyzing the expression of key molecules and for examining their production at the genetic level. The work focuses on the analysis and mapping of molecules produced by cells and tissues, and on the molecular biology underlying their expression. The traditional methods range from the histopathological and the immunocytochemical to SDS-PAGE, Western blotting, and enzyme zymography. Newer and more specialized techniques for analyzing the genetic aspects of metastasis include in situ hybridization to localize mRNAs, FISH, CGH, methylation analysis of CpG islands, RT-PCR, and differential display. The second volume of this set, Analysis of Cell Behavior In Vitro and In Vivo, moves to the level of living cells and tissues to present methodologies applicable to examining metastatic behavior in vitro and in the whole animal. Comprehensive and authoritative, the two volumes of Metastasis Research Protocols constitute a gold-standard collection of readily reproducible methods for understanding the metastatic cascade-first at the cellular and molecular levels, then at the level of the whole organism-responsible for the spread of cancer and for developing novel strategies to combat its spread