gebhart/patrepeval huggingface dataset:
Structure and Function of the Glycine Receptor and Related Nicotinicoid Receptors (2004)

Although many of the details of GlyR dynamics still remain elusive, the extensive studies conducted on GlyR and other members of the nicotinicoid superfamily in recent years provide us with an emerging picture of the structure and function of these receptors. As novel studies continue to examine these receptors, we are confident that these ion channels will reveal their molecular mechanisms. These details are significant in that they will allow us to develop novel therapeutics and pharmacological tools to modulate channel activity in the central nervous system.
Klebsiella pneumoniae OmpA Confers Resistance to Antimicrobial Peptides (2008)

A Klebsiella pneumoniae ompA mutant was more susceptible to antimicrobial peptides (APs) than the wild type. Susceptibility did not result from surface changes other than the absence of OmpA. Our data suggest that OmpA is implicated in the activation of yet-unknown systems dedicated to ameliorating AP cytotoxicity.
A Test for Creutzfeldt–Jakob Disease Using Nasal Brushings (2014)

In this preliminary study, RT-QuIC testing of olfactory epithelium samples obtained from nasal brushings was accurate in diagnosing Creutzfeldt-Jakob disease and indicated substantial prion seeding activity lining the nasal vault. (Funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and others.).
Purification of interferon from mouse Ehrlich ascites tumor cells. (1978)

Interferon production was induced in mouse Ehrlich ascites tumor cells by infection with Newcastle disease virus. The interferon produced was purified by precipitation with ammonium sulfate, chromatography on carboxymethyl-Sephadex, treatment with blue dextran and polyethylene glycol, gel filtration on Bio-Gel P-60 and Bio-Gel P-200, chromatography on phosphocellulose, isoelectric focusing, and chromatography on octyl-Sepharose. The specific activity of the product was 1.6 x 10(9) NIH mouse interferon reference standard units/mg of protein. Electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulfate indicated that the apparent molecular weight of the interferon-active material ranged from 25,000 to 35,000. As revealed by staining the gels with Coomassie brilliant blue, the interferon activity co-migrated with the major, broad protein band. Minor, stainable bands of proteins were free of interferon activity and their apparent molecular weight was smaller than 12,000.
Applications of neural networks in quantitative structure-activity relationships of dihydrofolate reductase inhibitors (1991)

Back propagation neural networks is a new technology useful for modeling nonlinear functions of several variables. This paper explores their applications in the field of quantitative structure-activity relationships. In particular, their ability to fit biological activity surfaces, predict activity, and determine the "functional forms" of its dependence on physical properties is compared to well-established methods in the field. A dataset of 256 5-phenyl-3,4-diamino-6,6-dimethyldihydrotriazines that inhibit dihydrofolate reductase enzyme is used as a basis for comparison. It is found that neural networks lead to enhanced surface fits and predictions relative to standard regression methods. Moreover, they circumvent the need for ad hoc indicator variables, which account for a significant part of the variance in linear regression models. Additionally, they lead to the elucidation of nonlinear and "cross-products" effects that correspond to trade-offs between physical properties in their effect on biological activity. This is the first demonstration of the latter two findings. On the other hand, due to the complexity of the resulting models, an understanding of the local, but not the global, structure-activity relationships is possible. The latter must await further developments. Furthermore, the longer computational time required to train the networks is somewhat inconveniencing, although not restrictive.
Polyethylene Glycol as an Embedment for Microscopy and Histochemistry (1993)

An Overview of the Polyethylene Glycols (M.R. Leous). Polyethylene Glycol-Celloidin Mixture for Histological and Histochemical Studies (I.A. Efimov). Polyethylene Glycol in Immunocytochemistry and Enzyme Histochemistry (J. Mowery). PEG-Embedding and Subsequent De-Embedding as a New Method for Multi-Purposes in Electron Microscopy (H. Kondo). Using PEG Sections to Screen Monoclonal Antibodies (J.B.L. Bard and A.S.A. Ross). Application of PEG Sections for In Situ Hybridization Studies (A. Alvarez-Buylla and D.F. Clayton). A New Method for Transfer of Polyethylene Glycol Sections onto Silanated Slides for Immunocytochemistry (K.X. Gao). Diethylene Glycol Distearate (DGD): An Alternative to PEG as a Removable Embedment (D.G. Capco).
Excitatory Amino Acid Transmitters (1981)

Excitatory Amino Acid Transmitters, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/pharmtox/21/1/annurev.pa.21.040181.001121-1.gif
Definition of the Differentiated Services Field (DS Field) in the IPv4 and IPv6 Headers (1998)

Differentiated services enhancements to the Internet protocol are intended to enable scalable service discrimination in the Internet without the need for per-flow state and signaling at every hop.A variety of services may be built from a small, well-defined set of building blocks which are deployed in network nodes.The services may be either end-to-end or intra-domain; they include both those that can satisfy quantitative performance requirements (e.g., peak bandwidth) and those based on relative performance (e.g., "class" differentiation).Services can be constructed by a combination of:-setting bits in an IP header field at network boundaries (autonomous system boundaries, internal administrative boundaries, or hosts), -using those bits to determine how packets are forwarded by the nodes inside the network, and -conditioning the marked packets at network boundaries in accordance with the requirements or rules of each service.Nichols, et.al.
4-Anilino-3-quinolinecarbonitriles: An Emerging Class of Kinase Inhibitors (2002)

The first potent selective small molecule inhibitor of a protein kinase was reported in 1994 by Parke-Davis. PD-153035, 4-(3-bromoanilino)-6,7-dimethoxyquinazoline, is an ATP competitive inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFr), with no appreciable inhibitory activity against several other kinases. Subsequent structural elaboration of PD-153035 led to several 4-anilinoquinazolines that are currently in various stages of clinical trials for the treatment of kinase-mediated diseases. A homology model of EGFr with PD-153035 suggested that the 3-nitrogen atom of the quinazoline ring binds a water molecule. It was envisioned that this nitrogen atom could be replaced by a carbon atom containing an electron-withdrawing group. This critical observation by a group at Wyeth led to the identification of 4-(3-bromoanilino)-6,7-dimethoxy-3-quinolinecarbonitrile as an EGFr inhibitor. It was subsequently established that variation of the substituents on the 4-anilino group of the 6,7-dimethoxy-3-quinolinecarbonitrile changed the kinase specificity from EGFr to other kinases including Src and MEK. The 3-quinolinecarbonitrile template was also utilized to develop an irreversible inhibitor of EGFr, EKB-569, currently in clinical trials for the treatment of cancer. Further manipulation of the 3-quinolinecarbonitrile core provided tricyclic analogs, with the most potent kinase inhibitory activity observed with a benzo[g]quinoline-3-carbonitrile ring system. It was also found that 3-quinolinecarbonitriles with a 7-thiophene or phenyl substituent were potent Src kinase inhibitors.
Estrogen Receptor-Alpha 36 Mediates Mitogenic Antiestrogen Signaling in ER-Negative Breast Cancer Cells (2012)

It is prevailingly thought that the antiestrogens tamoxifen and ICI 182, 780 are competitive antagonists of the estrogen-binding site of the estrogen receptor-alpha (ER-α). However, a plethora of evidence demonstrated both antiestrogens exhibit agonist activities in different systems such as activation of the membrane-initiated signaling pathways. The mechanisms by which antiestrogens mediate estrogen-like activities have not been fully established. Previously, a variant of ER-α, EP-α36, has been cloned and showed to mediate membrane-initiated estrogen and antiestrogen signaling in cells only expressing ER-α36. Here, we investigated the molecular mechanisms underlying the antiestrogen signaling in ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells that express high levels of endogenous ER-α36. We found that the effects of both 4-hydoxytamoxifen (4-OHT) and ICI 182, 780 (ICI) exhibited a non-monotonic, or biphasic dose response curve; antiestrogens at low concentrations, elicited a mitogenic signaling pathway to stimulate cell proliferation while at high concentrations, antiestrogens inhibited cell growth. Antiestrogens at l nM induced the phosphorylation of the Src-Y416 residue, an event to activate Src, while at 5 µM induced Src-Y527 phosphorylation that inactivates Src. Antiestrogens at 1 nM also induced phosphorylation of the MAPK/ERK and activated the Cyclin D1 promoter activity through the Src/EGFR/STAT5 pathways but not at 5 µM. Knock-down of ER-α36 abrogated the biphasic antiestrogen signaling in these cells. Our results thus indicated that ER-α36 mediates biphasic antiestrogen signaling in the ER-negative breast cancer cells and Src functions as a switch of antiestrogen signaling dependent on concentrations of antiestrogens through the EGFR/STAT5 pathway.
Detection of a Paternally Inherited Fetal Mutation in Maternal Plasma by the Use of Automated Sequencing (2006)

The discovery of circulating fetal DNA in maternal blood has been an encouraging step forward in the prenatal diagnostic field. It has opened up the possibility of development of a noninvasive method for the genetic analysis of the fetus. Many techniques have been applied to the study of this fetal DNA, but automated sequencing has been seldom used. The intention of this study was to use the automated sequencing technique for the detection of a paternally inherited fetal mutation in maternal plasma. Maternal plasma samples from a pregnant woman, whose husband had a mutation (Q134X) in the RP2 gene, which is located in the X-chromosome, were collected at two different gestational ages (10th and 19th week of gestation) in order to determine whether the paternally inherited fetal mutation could be detected by automated sequencing. Restriction analysis was also performed to confirm the results. The fetal mutation was clearly detected in the maternal plasma by the use of automated sequencing. The automated sequencing enables the possibility of analyzing fetal sequences, at a nucleotide level, in order to detect mutations or polymorphisms which are distinguishable from maternal sequences.
Delivery Strategies for Antisense Oligonucleotide Therapeutics (2017)

PrefaceOverview of Antisense Oligonucleotide Therapeutics and DeliveryDisrupting the Flow of Genetic Information with Antisense Oligodeoxynucleotides: Research and Therapeutic Applications, D. Kregenow, M.Z. Ratajczak, and A. GewirtzCellular Delivery of Ribozymes, D.A. Elkins and J.J. RossiImproved Structural Design and Cellular Uptake of GT-Rich Triplex-Forming Oligonucleotides, N. Choudhary, J.S. Bishop, K. Jayaraman, and J.K. Guy-CaffeyPharmacokinetic and Distribution StudiesPharmacokinetics and Delivery of Oligonucleotides to the Brain, L. Neckers, D.A. Geselowitz, and C. ChavanyIn Vivo Pharmacokinetics of Oligonucleotides Following Administration by Different Routes, V.V. Vlassov, L.A. Yakubov, V. Karamyshev, L. Pautova, E. Rykova, and M. NechaevaImproving Biological Stability of OligonucleotidesNuclease-Resistant Nucleic Acid Therapeutics, E. WickstromSelf-Stabilized Oligonucleotides as Novel Antisense Agents, S. Agrawal, J. Temsamani, and J. TangCircular Oligonucleotides as Potential Modulators of Gene Expression, E.T. KoolPeptide Nucleic Acids as Antisense Therapeutic Agents, J.C. Hanvey and L.E. BabissStabilized RNA Analogues for Antisense and Ribozyme Applications, H. Arup, O. Heindenreich, F. EcksteinImproving Membrane Transport and Targeted Delivery of Antisense OligonucleotidesUptake and Localization of Phosphodeister and Chimeric Oligodeoxynucleotides in Normal and Leukaemic Primary Cells, A. KreigOligonucleotide Transport across Membranes and into Cells: Effects of Chemical Modifications, J. Hughes, A. Avroutskaya, H.M. Sasmoor, C.J. Guinosso, P.D. Cook, and R.L. JulianoLiposomes as a Delivery System for Antisense and Ribozyme Compounds, A. Thierry and G.B. TakleIntracellular Delivery of Oligonucleotides with Cationic Liposomes, C.F. BennettThe Delivery of Oligonucleotides Using pH-Sensitive Liposomes, C. Ropert, P. Couvreur, and C. MalvyEnhancing Endsosomal Exit of Nucleic Acids Using pH-Sensitive Viral Fusion Peptides, B. Oberhauser, C. Plank , and E. WagnerTargeted Delivery of Anti-Hepatitis B Antisense Oligonucleotides, E.P. Carmichael, H.C. Chiou, M.A. Findeis, G.L. Spitalny, and J.R. MerwinDesign, Synthesis, and Cellular Delivery of Antibody Antisense Oligonucleotide Conjugates for Cancer Therapy, C.S.R. Gooden and A.A. Epenetos
Imaging true 3D endoscopic anatomy by incorporating magnetic tracking with optical coherence tomography: proof-of-principle for airways (2010)

Endoscopic imaging using optical coherence tomography (OCT) has been demonstrated as clinically useful in the assessment of human airways. These airways have a complex 3D structure, bending, tapering and bifurcating. Previously published 3D OCT reconstructions have not accounted for changes in the orientation and trajectory of the endoscopic probe as it moves through the airway during imaging. We propose a novel endoscopic setup incorporating a magnetic tracking system that accounts for these changes, yielding reconstructions that reveal the true 3D nature of the imaged anatomy. We characterize the accuracy of the system, and present the first published magnetic tracker-assisted endoscopic OCT reconstructions using a phantom airway.
Hinge-loss Markov Random Fields: Convex Inference for Structured Prediction (2013)

Graphical models for structured domains are powerful tools, but the computational complexities of combinatorial prediction spaces can force restrictions on models, or require approximate inference in order to be tractable. Instead of working in a combinatorial space, we use hinge-loss Markov random fields (HL-MRFs), an expressive class of graphical models with log-concave density functions over continuous variables, which can represent confidences in discrete predictions. This paper demonstrates that HL-MRFs are general tools for fast and accurate structured prediction. We introduce the first inference algorithm that is both scalable and applicable to the full class of HL-MRFs, and show how to train HL-MRFs with several learning algorithms. Our experiments show that HL-MRFs match or surpass the predictive performance of state-of-the-art methods, including discrete models, in four application domains.
Activation of Toll‐like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP‐105) sufficiently enhances immune responses against tumors (2008)

The cell wall skeleton of Mycobacterium bovis BCG has been investigated as an immunopotentiating adjuvant for immuno-therapy of malignant tumors via Toll-like receptor (TLR) 2 and TLR4. However, due to its high molecular weight, highly complicated lipoglycan structure, and complicated purification and isolation procedure, its exact structure-activity relationship has not been well established. We have newly isolated the cell wall skeleton from M. bovis BCG Tokyo (SMP-105) and examined the binding of SMP-105 with TLR. It was revealed that highly purified SMP-105 activates the nuclear factor-kB promoter in a TLR2-dependent manner, not a TLR4-dependent manner, using a reporter gene assay system. Peritoneal exudated cells of TLR2 and MyD88 knockout mice severely reduced the induction of tumor necrosis factor-alpha and interleukin-6 in the presence of SMP-105, whereas cells from TLR4 knockout mice produced similar levels of cytokines to wild-type mice. Dendritic cells and macrophages accumulated in the draining lymph nodes of treated mice. When mice were administered both SMP-105 and mitomycin C-inactivated Lewis lung carcinoma cells simultaneously, interferon-gamma-producing cells reacting to the tumor were increased distinctly in draining lymph nodes. When C57BL/6 mice, into which splenocytes from OT-I transgenic mice had been transferred, were administered with both SMP-105 and E.G7-OVA, OVA-specific cytotoxic T lymphocytes (CTL) increased markedly. Mice treated with SMP-105 and inactivated Lewis lung carcinoma cells suppressed the growth of implanted tumors. These results suggest that the activation of TLR2 by SMP-105 sufficiently enhanced immune responses, such as the number of interferon-gamma-producing cells and CTL, and prevented the growth of tumors without the contribution of TLR4.
S-Pixyl Analogues as Photocleavable Protecting Groups for Nucleosides (2002)

Several analogues of the 9-phenylthioxanthyl (S-pixyl) photocleavable protecting group have been synthesized, containing substituents on the 9-aryl ring and on the thioxanthyl backbone. Each analogue protected the 5'-hydroxy moiety of thymidine in good to excellent yield. The protected substrates were deprotected in 1:1 water:acetonitrile with irradiation at 300 nm, resulting in recovered thymidine in excellent yield, except for the nitro-substituted analogues which gave substantially lower yields. Substrates with 2,7-dibromo or 3-methoxy substitution on the thioxanthyl backbone were also deprotected efficiently with irradiation at 350 nm. Shorter irradiation times were observed in the less nucleophilic solvent mixture of 1:9 trifluoroethanol:acetonitrile, with no formation of secondary photooxidation products. Photodeprotection with high yields was also achieved in the absence of solvent, with no secondary photoproducts.
Circulating soluble tumor necrosis factor receptors, interleukin‐2 receptors, tumor necrosis factor α, and interleukin‐6 levels in rheumatoid arthritis. (1993)

Measurement of circulating sIL-2R, p55, and IL-6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.
64Cu-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-E{E[c(RGDfK)]2}2 (2008)

64Cu-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-E{E[c(RGDfK)2}2 (64Cu-DOTA-E{E[c(RGDfK)2}2) is an integrin-targeted molecular imaging agent developed for positron emission tomography (PET) imaging of tumor vasculature, tumor angiogenesis and osteoclasts (1). 64Cu is a positron emitter with a half-life (t½) of 12.7 hCellular survival, invasion, and migration control embryonic development, angiogenesis, tumor metastasis, and other physiologic processes (2, 3). Among the molecules that regulate angiogenesis are integrins which comprise a superfamily of cell adhesion proteins that form heterodimeric receptors for extracellular matrix (ECM) molecules (4, 5).These transmembrane glycoproteins consist of two noncovalently associated subunits, α and β (18 α- and 8 β-subunits in mammals), which are assembled into at least 24 α/β pairs. Several integrins, such as integrin αvβ3, have affinity for the arginine-glycine-aspartic acid (RGD) tripeptide motif, which is found in many ECM proteins. Expression of integrin αvβ3 receptors on endothelial cells is stimulated by angiogenic factors and environments. The integrin αvβ3 receptor is generally not found in normal tissue but it is strongly expressed in vessels with increased angiogenesis, such as tumor vasculature. It is significantly upregulated in certain types of tumor cells and in almost all tumor vasculature. Molecular imaging probes carrying the RGD motif that binds to the integrin αvβ3 can be used to image tumor vasculature and evaluate angiogenic response to tumor therapy (6, 7).Various RGD peptides in both linear and cyclic forms have been developed for in vivo binding to integrin αvβ3 (8). It has been hypothesized that cyclic RGD peptide may have a faster rate of receptor binding or a slower rate of dissociation from the integrin αvβ3 than linear single-RGD peptides (1). Chen et al. (9) evaluated a cyclic RGD peptide [c(RGDyK)] labeled with 64Cu or 18F in nude mice bearing breast tumor. They used DOTA for c(RGDyK) conjugation with 64Cu. 64Cu-DOTA-c(RGDyK) showed prolonged tumor radioactivity retention but persistent liver radioactivity. Wu et al. (1) suggested that a multimeric RGD peptide with more than two repeating cyclic RGD units would further enhance the affinity of the receptor−ligand interactions through the phenomenon of a polyvalency effect. They also suggested that the increase in molecular size might also prolong circulation time and reduce tumor washout rate as well. Consequently, Wu et al. (1) developed a tetrameric RGD peptide, 64Cu-DOTA-E{E[c(RGDfK)2}2, and they showed that this PET radioligand appeared to have high integrin avidity and favorable biokinetics in nude mice bearing human glioma.
Original image slicer designed for integral field spectroscopy with the near-infrared spectrograph for the James Webb Space Telescope (2006)

Integral field spectroscopy (IFS) provides a spectrum simultaneously for each spatial sample of an extended 2-D field. It consists of an integral field unit (IFU), which slices and rearranges the initial field along the entrance slit of a spectrograph. We present an original design of IFU based on the advanced image slicer concept. To reduce optical aberrations, pupil and slit mirrors are disposed in a fan-shaped configuration, which means that angles between incident and reflected beams on each element are minimized. The fan-shaped image slicer improves image quality in terms of wavefront error by a factor of 2 compared with a classical image slicer, and furthermore, it guaranties a negligible level of differential aberration in the field. As an example, we present the design LAM used for its proposal at the near-infrared spectrograph (NIRSpec/IFU) invitation of tender for the James Webb Space Telescope (JWST).