gebhart/patrepeval huggingface dataset:
Abstract 1221: Targeting interferon-λ1 with a stabilized dimer of anti-tumor Fab . (2013)

Abstract Background: The type-III interferons (IFNs), comprising IFN-λ1, IFN-λ2, and IFN-λ3, are functionally similar to the type-I IFN-α in eliciting anti-viral, anti-tumor, and immune-modulating activities. Due to its more restricted cellular targets, IFN-λ is being considered as a potential alternative to existing therapeutic regimens based on IFN-α, whose adverse effects in patients limit its use. The development of antibody-targeted IFN-λ may further improve its safety, potency and pharmacokinetics. Methods: We generated three DOC-AND-LOCKTM (DNLTM) complexes, designated (E1)-λ1, (15)-λ1, and (C2)-λ1, by conjugating IFN-λ1 site-specifically to a stabilized dimer of humanized Fab derived from hRS7 (anti-Trop-2), hMN-15 (anti-CEACAM6), and hL243 (anti-HLA-DR), respectively, which were affinity-purified and evaluated in human malignant cell lines of cervix (ME-180), colon (HT-29), esophagus (TE-11, T.Tn), lung (SK-MES-1, A549), liver (HepG2, Huh-7), and skin (A375). Results: As determined by flow cytometry, Trop-2 was highly expressed on the surface of ME-180, TE-11, and T.Tn; moderately on SK-MES-1 and HT-29; and negligibly on HepG2, Huh-7, A549, and A375. In comparison, CEACAM6 was undetectable on SK-MES-1 and A375, but positive on the remaining 7 cell lines, yet at a considerably lower level than Trop-2. Targeting of these immunocytokines to antigen-expressing cells markedly increased the amount of IFN-λ1 localized at the cell surface, as demonstrated by (E1)-λ1 on ME-180 (Trop-2+), (15)-λ1 on HepG2 (CEACAM6+), and (C2)-λ1 on A375 (HLA-DR+), respectively. In MTS assays, (E1)-λ1 inhibited the in vitro proliferation of ME-180, SK-MES-1, and TE-11, with EC50 &amp;lt;1 pM, which was 1,000-fold more potent than commercial IFN-λ1. Likewise, the anti-proliferation activity of (15)-λ1 was enhanced ∼100-fold in ME-180 and TE-11, but not in CEACAM6-negative SK-MES-1. The observed potency was further substantiated by enhanced cell signaling, including STAT phosphorylation and MHC-I up-regulation induced by (15)-λ1 in HepG2 cells. In the Pk study, (E1)-λ1 showed a mean residence time of 12 h with a T1/2 of 8.6 h, and clearance of 2.2 ml/h in mouse serum, which is comparable to PEG-IFN-λ1. Conclusions: These promising results, attributable to increased localization and stronger binding to antibody-targeted cells, warrant further exploration of these novel immunocytokines as potential cancer therapeutics. Citation Format: Donglin Liu, Edmund A. Rossi, Thomas M. Cardillo, David M. Goldenberg, Chien-Hsing Chang. Targeting interferon-λ1 with a stabilized dimer of anti-tumor Fab . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1221. doi:10.1158/1538-7445.AM2013-1221
High yield conversion of doxorubicin to 2-pyrrolinodoxorubicin, an analog 500-1000 times more potent: structure-activity relationship of daunosamine-modified derivatives of doxorubicin. (1996)

A convenient, high yield conversion of doxorubicin to 3'-deamino-3'-(2''-pyrroline-1''-yl)doxorubicin is described. This daunosamine-modified analog of doxorubicin is 500-1000 times more active in vitro than doxorubicin. The conversion is effected by using a 30-fold excess of 4-iodobutyraldehyde in anhydrous dimethylformamide. The yield is higher than 85%. A homolog of this compound, 3'-deamino-3'-(1'',3''-tetrahydropyridine-1''-yl)doxorubicin, was also synthesized by using 5-iodovaleraldehyde. In this homolog, the daunosamine nitrogen is incorporated into a six- instead of a five-membered ring. This analog was 30-50 times less active than its counterpart with a five-membered ring. A similar structure-activity relationship was found when 3'-deamino-3'-(3''-pyrrolidone-1''-yl)doxorubicin (containing a five-membered ring) and 3'-deamino-3'-(3''-piperidone-1''-yl)doxorubicin (with a six-membered ring) were tested in vitro, the former being 5 times more potent than the latter. To further elucidate structure-activity relationships, 3'-deamino-3'-(pyrrolidine-1''-yl)doxorubicin, 3'-deamino-3'-(isoindoline-2''-yl)doxorubicin, 3'-deamino-3'-(2''-methyl-2''-pyrroline-1''-yl)doxorubicin, and 3'-deamino-3'-(3''-pyrroline-1''-yl)doxorubicin were also synthesized and tested. All the analogs were prepared by using reactive halogen compounds for incorporating the daunosamine nitrogen of doxorubicin into a five- or six-membered ring. These highly active antineoplastic agents can be used for incorporation into targeted cytotoxic analogs of luteinizing hormone-releasing hormone intended for cancer therapy.
VEGF, a prosurvival factor, acts in concert with TGF-β1 to induce endothelial cell apoptosis (2006)

VEGF and TGF-beta1 are potent angiogenesis inducers with opposing effects on endothelial cells. TGF-beta1 induces apoptosis; VEGF protects endothelial cells from apoptosis. We found that TGF-beta1 promotes endothelial cell expression of FGF-2, which up-regulates VEGF synthesis. Inhibition of VEGF signaling through VEGF receptor 2 (flk-1) abrogates TGF-beta1-induced apoptosis and p38(MAPK) activation. Inhibition of p38(MAPK) blocks TGF-beta1-induced apoptosis, showing that VEGF/flk-1-mediated activation of p38(MAPK) is required for TGF-beta1 induction of apoptosis. In the absence of TGF-beta1, VEGF activates p38(MAPK) and promotes endothelial cell survival. However, in context with TGF-beta1, VEGF/flk-1-mediated activation of p38(MAPK) results in apoptosis. Thus, cross-talk between TGF-beta1 and VEGF signaling converts VEGF/flk-1-activated p38(MAPK) into a proapoptotic signal. This finding illustrates an unexpected role of VEGF and indicates that VEGF can be pharmacologically converted into an apoptotic factor, a novel approach to antiangiogenesis therapy.
A Cox-2 Promoter-Based Replication-Selective Adenoviral Vector to Target the Cox-2-Expressing Human Bladder Cancer Cells (2004)

The present study demonstrated both specificity and efficacy of AdE3-cox2-327, a selectively replicated adenovirus, toward the Cox-2-expressing bladder cancer cells in vitro and in vivo. We also found that CAR expression in the target cancer cells is an important factor for the efficacy of selectively replicated adenovirus-based gene therapy.
New Woes May Trigger Another Shakeout for U.S. Dye Producers (1993)

RETURN TO ISSUEPREVNewsNEXTNew Woes May Trigger Another Shakeout for U.S. Dye ProducersSurge in imports from China and India, growing regulatory pressure to control pollution are squeezing companiesMARC S. REISCHView Author Information C&EN Northeast News BureauCite this: Chem. Eng. News 1993, 71, 27, 9–11Publication Date (Print):July 5, 1993Publication History Published online11 November 2010Published inissue 5 July 1993https://pubs.acs.org/doi/10.1021/cen-v071n027.p009https://doi.org/10.1021/cen-v071n027.p009newsACS PublicationsCopyright © 1993 American Chemical SocietyArticle Views4Altmetric-Citations-LEARN 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 SUBJECTS:Dyes and pigments Get e-Alerts
Sensor Selection for Cooperative Spectrum Sensing (2008)

This article considers spectrum-on-demand in a cellular system. A communication system that wants to access spectrum to which it does not own a license must perform spectrum sensing to identify spectrum opportunities, and to guarantee that it does not cause unacceptable interference to the license owner. Because a single sensor may be in a fading dip, cooperative sensing among multiple sensors which experience uncorrelated fading is required to guarantee reliable sensing performance. At the same time, as few sensors as possible should be used to reduce the battery consumption, while still employing enough many for the sensing to be reliable. Since shadow fading is correlated for closely spaced sensors, it is desired to select sensors which are sufficiently spatially separated. The present article addresses the problem of selecting appropriate sensors from a candidate set to engage in cooperative sensing, using different degrees of knowledge about the sensor positions. Three different algorithms for sensor selection are presented and evaluated by means of simulation. It is shown that all algorithms outperform random selection of the sensors.
Selective Inhibition of Ras-dependent Cell Growth by Farnesylthiosalisylic Acid (1995)

S-trans,trans-Farnesylthiosalicylic acid (FTS) is a novel farnesylated rigid carboxylic acid derivative. In cell-free systems, it acts as a potent competitive inhibitor (Ki = 2.6 microM) of the enzyme prenylated protein methyltransferase (PPMTase), which methylates the carboxyl-terminal S-prenylcysteine in a large number of prenylated proteins including Ras. In such systems, FTS inhibits Ras methylation but not Ras farnesylation. Inhibition of the PPMTase by FTS in homogenates or membranes of a variety of tissues and cell lines is inferred from a block in the methylation of exogenously added substrates such as N-acetyl-S-trans,trans-farnesyl-L-cysteine and of endogenous substrates including small GTP-binding proteins. FTS can also inhibit methylation of these proteins in intact cells (e.g. in Rat-1 fibroblasts, Ras-transformed Rat-1, and B16 melanoma cells). Unlike in cell-free systems, however, relatively high concentrations of FTS (50-100 microM) are required for partial blocking (10-40%) of protein methylation in the intact cells. Thus, FTS is a weak inhibitor of methylation in intact cells. Because methylation is the last step in the processing of Ras and related proteins, FTS is not likely to affect steps that precede it, e.g. protein prenylation. This may explain why the growth and gross morphology of a variety of cultured cell types (including Chinese hamster ovary, NIH3T3, Rat1, B16 melanoma, and PC12) is not affected by up to 25 microM FTS and is consistent with the observed lack of FTS-induced cytotoxicity. Nevertheless, FTS reduces the levels of Ras in cell membranes and can inhibit Ras-dependent cell growth in vitro, independently of methylation. It inhibits the growth of human Ha-ras-transformed cells (EJ cells) and reverses their transformed morphology in a dose-dependent manner (0.1-10 microM). The drug does not interfere with the growth of cells transformed by v-Raf or T-antigen but inhibits the growth of ErbB2-transformed cells and blocks the mitogenic effects of epidermal and basic fibroblast growth factors, thus implying its selectivity toward Ras growth signaling, possibly via modulation of Ras-Raf communication. Taken together, the results raise the possibility that FTS may specifically interfere with the interaction of Ras with a farnesylcysteine recognition domain in the cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. (1994)

Transgenic mice expressing mutant Cu,Zn superoxide dismutase (SOD), containing a substitution of glycine at position 93 by alanine, develop disease prevalently affecting motor neurons. Light microscopical and ultrastructural studies reveal that the earliest pathological features are microvesiculation of large neurons of the anterior horns of the spinal cord. These vacuoles originate from dilation of rough endoplasmic reticulum and from degenerating mitochondria. At the end stage of the disease, the microvesicular pattern gives way to atrophic anterior horns showing severe neuronal depletion and hyaline, filamentous inclusions in some of the surviving neurons. Posterior horn neurons and dorsal root ganglia are not affected. With disease progression, moderate degeneration of anterior and lateral columns, severe degeneration of anterior roots, and mild degeneration in posterior columns and roots become apparent. This study shows that a mutation in SOD, known to occur in a percentage of familial amyotrophic lateral sclerosis patients, may affect only selective neuronal populations, although SOD is a ubiquitous enzyme.
Interactive diagnosis and repair of decision-theoretic models (2002)

The authors present an intuitive, interactive method for diagnosing and repairing a formal decision-theoretic model, and describe the role of this method in interpretive value analysis (IVA), a general framework for modeling choices in expert systems that is at once formal and transparent. IVA's interpretation concepts provide an internally consistent vocabulary based on value theory for talking about decisions. IVA's explanation component explains the operation-by-operation computation of a comparison of two alternatives, using interpretation concepts, operation explainers, and the difference-function topology. IVA's diagnosis-and-repair method uses this explanation component, along with modules for suggesting, repairing, and verifying the integrity of parameter values, to assist users with modifying models that deviate from their preferences. This approach suggests that knowledge engineers can retain the benefits of decision theory's formal foundation without compromising intuitive explanation and knowledge acquisition.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hydroxyethyl Starch Antibodies in Humans (1998)

Hydroxyethyl starch (HES) is a plasma expander used for perioperative IV fluid management, as well as for resuscitation from trauma and shock.HES is very well tolerated, and the incidence of anaphylactic reactions is lower than with dextran or gelatin. Dextran anaphylaxis is caused by circulating dextran-reactive antibodies (ABs) of the immunoglobin G (IgG) class found in most adults. Histamine release from mast cells induces adverse reactions after gelatin infusion. The cause of adverse reactions due to HES is not yet clear. To investigate AB formation due to HES, we collected sera of 1004 patients at least 14 days after starch administration. Using a highly sensitive enzyme-linked immunoabsorbent assay technique, we found one patient with a low 1:10 titer of HES-reactive ABs (immunoglobin M [IgM] class). Despite repeated HES infusions, no clinical reaction could be detected in this patient. On the basis of a binomial distribution, a one-tailed confidence interval (99%) was used to calculate the percentage of the occurrence of ABs in general with maximum of 33 in 10,000 persons (IgM) and 23 in 10,000 persons (IgG). We suggest that HES-reactive ABs are extremely rare and that they do not necessarily induce anaphylaxis. Other mechanisms may be responsible for adverse reactions due to HES. Implications: The frequency of antibody formation due to hydroxyethyl starch, a commonly used plasma expander, was prospectively investigated in 1004 patients. Only one patient showed transient antibody formation, which was not harmful to the patient. This low antigenicity could explain the excellent tolerance of hydroxyethyl starch compared with other plasma expanders. (Anesth Analg 1998;86:1123-6)
Alteration of in vivo cytokine gene expression in mice infected with a molecular clone of the defective MAIDS virus. (1994)

The discovery of T helper type 1 (Th1) and T helper type 2 (Th2) phenotypes within the CD4+ T-lymphocyte population has allowed for further elucidation of the roles the T cells play in regulation of humoral and cellular immunity. It is suggested that differential activation of the CD4+ subsets, particularly up-regulation of the Th2 cell and down-regulation of the Th1 cell, may be associated with diseases as diverse as AIDS and asthma. We report herein that by using the polymerase chain reaction to analyze the kinetics of in vivo cytokine- and virus-specific gene expression, we can show that mice infected with the molecularly cloned MAIDS defective virus 1/27/A BM5 exhibit an alteration in cytokine gene expression that closely parallels an increase in spleen cell numbers, an increase in IgM production, a decrease in the stimulation index, and an increase in defective-virus gene expression in these mice. As has been suggested to be true for human AIDS, the observed alteration of cytokine gene expression suggests that a pattern of expression similar to that produced by Th2 cells may also have a role in the development of MAIDS.
Radical oxidation of germanium for interface gate dielectric GeO2 formation in metal-insulator-semiconductor gate stack (2009)

GeO 2 was grown by a slot-plane-antenna (SPA) high density radical oxidation, and the oxidation kinetics of radical oxidation GeO2 was examined. By the SPA radical oxidation, no substrate orientation dependence of growth rate attributed to highly reactive oxygen radicals with low oxidation activation energy was demonstrated, which is highly beneficial to three-dimensional structure devices, such as multigate field-effect transistors, to form conformal gate dielectrics. The electrical properties of an aluminum oxide (Al2O3) metal-oxide-semiconductor gate stack with a GeO2 interfacial layer were investigated, showing very low interface state density (Dit), 1.4×1011 cm−2 eV−1. By synchrotron radiation photoemission spectroscopy, the conduction and the valence band offsets of GeO2 with respect to Ge were estimated to be 1.2±0.3 and 3.6±0.1 eV, which are sufficiently high to suppress gate leakage.
Instantaneous Reactive Power p-q Theory and Power Properties of Three-Phase Systems (2005)

This paper investigates how power phenomena and properties of three-phase systems are described and interpreted by the Instantaneous Reactive Power (IRP) p-q Theory. This paper demonstrates that this theory misinterprets power properties of electrical systems or provides some results that at least defy a common sense or meaning of some notions in electrical engineering. For example, it suggests the presence of an instantaneous reactive current in supply lines of purely resistive loads and the presence of an instantaneous active current in supply lines of purely reactive loads. Moreover, it suggests that line currents of linear loads with sinusoidal supply voltage contain a nonsinusoidal component. This paper shows, moreover, that the IRP p-q Theory is not capable to identify power properties of three-phase loads instantaneously. A pair of instantaneous values of p and q powers does not allow us to conclude whether the load is resistive, reactive, balanced, or unbalanced. It is known that a load imbalance reduces power factor. However, the IRP p-q Theory does not identify the load imbalance as the cause of power factor degradation.
Overcoming food allergy through acquired tolerance conferred by transfer of Tregs in a murine model (2011)

We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy.
Surface confined ionic liquid as a stationary phase for HPLC (2006)

Trimethoxysilane “ionosilane” derivatives of room temperature ionic liquids based on alkylimidazolium bromides were synthesized for attachment to silica support material. The derivatives 1-methyl-3-(trimethoxysilylpropyl)imidazolium bromide and 1-butyl-3-(trimethoxysilylpropyl)imidazolium bromide were used to modify the surface of 3 µm diameter silica particles to act as the stationary phase for HPLC. The modified particles were characterized by thermogravimetric analysis (TGA) and 13C and 29Si NMR spectroscopies. The surface modification procedure rendered particles with a surface coverage of 0.84 µmol m−2 for the alkylimidazolium bromide. The ionic liquid moiety was predominantly attached to the silica surface through two siloxane bonds of the ionosilane derivative (63%). Columns packed with the modified silica material were tested under HPLC conditions. Preliminary evaluation of the stationary phase for HPLC was performed using aromatic carboxylic acids as model compounds. The separation mechanism appears to involve multiple interactions including ion exchange, hydrophobic interaction, and other electrostatic interactions.
A high level synthesis tool for systolic designs (2003)

The authors present DECOMPOSER, a high-level synthesis tool for automating the design of systolic systems. DECOMPOSER takes as inputs a hierarchical description of the computation to be performed and some hint as to how it is to be performed. The computation description is in the form of a parameterized DAG (directed acyclic graph) so that different problem sizes can be handled. The hit is in the form of marking information for that DAG. DECOMPOSER produces a detailed report on the hardware requirements for the specified computation. In particular, the structure of each computation node, how the computation nodes are connected, and the input and output sequences are given. The information is passed to other tools in the tool set so that ultimately a layout description file in suitable format (e.g. CIF) can be generated for the architecture performing the computation derived by DECOMPOSER.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Strategies in transgenic animal science (1995)

Part I: General Transgenic Strategies Transgenic mouse strategies: embryology and animal science Preimplantation rat embryology: chimeric and transgenic strategies Nonrodent transgenic strategies Embryonic stem cell strategies: beyond the mouse model Part II: Transgenic Strategies in Biomedical Research Transgenic strategy for studying viral pathogenesis Strategies for studying cardiovascular diseases in transgenic and gene-targeted mice Strategies in the development of transgenic animal models for fl-amyloid-related neuropathologies of Alzheimer's disease Transgenic strategies used to study diabetes and obesity Transgenic strategies for satudying cholesterol metabolism Transgenic strategies for studying autoimmunity Mouse models of human genetic diseases and the develeopment of human gene therapy protocols Transgenic strategies for studying poliovirus pathogenesis and immunology Part III: Specialized Applications of Transgenics in Research Transgenic strategies in toxicology Trans-immortalization strategies in transgenics The H-2K tsA58 transgenic mouse as a single source of a wide range of conditionally immortal cell lines Index