gebhart/patrepeval huggingface dataset:
Molybdate-stabilized nonactivated glucocorticoid-receptor complexes contain a 90-kDa non-steroid-binding phosphoprotein that is lost on activation. (1986)

We have used a monoclonal antibody to purify glucocorticoid-receptor complexes from WEHI-7 mouse thymoma cells. Molybdate-stabilized, nonactivated complexes were found to contain two distinct proteins which could be separated by polyacrylamide gel electrophoresis under denaturing and reducing conditions. One of the proteins, 100 kDa, was labeled when cytosol was incubated with the affinity ligand [3H]dexamethasone 21-mesylate. The second protein, 90 kDa, was not labeled. Several lines of evidence, including Western blot analysis of purified nonactivated complexes, indicate that only the 100-kDa protein is directly recognized by the antibody. The 90-kDa protein appears to be purified as a component of the nonactivated complex due to noncovalent association with the 100-kDa protein. Both the 100-kDa and 90-kDa components of the nonactivated complex become labeled with 35S when cells are grown in medium containing [35S]methionine. Using cells labeled in this manner, we have shown that activated (i.e. DNA-binding) cytosolic complexes, formed by warming either in intact cells or under cell-free conditions, contain only the 100-kDa protein. Complexes extracted from nuclei of warmed cells similarly contain only the 100-kDa protein. These results indicate that the 100-kDa and 90-kDa components of nonactivated complexes separate upon activation. Purification of nonactivated complexes from cells grown in medium containing [32P]orthophosphoric acid indicates that both the 100-kDa and 90-kDa components are phosphoproteins which can be labeled with 32P. Therefore, resolution of the two proteins will be essential in order to determine whether the receptor is dephosphorylated on activation.
Surface properties of an amphiphilic peptide hormone and of its analog: corticotropin-releasing factor and sauvagine. (1983)

Synthetic corticotropin (adrenocorticotropic hormone)-releasing factor [CRF; for the sequence, see Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981) Science 213, 1394-1397] in aqueous solution exists predominantly as a random coil. At concentrations greater than 1 microM, the peptide shows a tendency to self-aggregate with a concurrent slight increase in the apparent alpha-helical content as measured by the CD spectrum. The alpha-helix formed by this molecule is highly amphiphilic--i.e., the hydrophilic and hydrophobic regions are segregated on opposite faces of the helix. As predicted from the potential amphiphilic structure, CRF binds avidly to the surface of single bilayer egg phosphatidylcholine vesicles. This binding appears to obey a simple Langmuir isotherm with the following parameters: Kd = 1.3 +/- 0.6 X 10(-7) M and capacity at saturation (N) = 11.0 +/- 1.0 mmol of peptide per mol of phospholipid. CRF also readily forms an insoluble monolayer at the air-water interface. The monolayer is composed of monomers of the hormone with molecular areas, A'0 = 22 A2 per amino acid, suggesting a compact secondary structure. Judged from the collapse pressure (19.0 +/- 0.1 dyne/cm; 1 dyne = 10 microN) of the monolayer, the amphiphilicity of CRF approximates that of plasma apolipoproteins, a class of proteins of the most pronounced amphiphilic character. These results suggest that the binding of CRF to the cell membrane is accompanied by the induction of an alpha-helical secondary structure and it is this predominantly helical form that is the biologically active form of the peptide.
NEONATAL NARCOTIC ADDICTION: 10 YEAR OBSERVATION (1971)

During the 10-year period 1960 through 1969, 384 infants were born to 382 heroin addicted mothers. One hundred ninety (49.4%) of the infants were under 2,500 gm in weight. Seventy -seven (40%) of these were low weight for date infants. Two hundred fifty-nine (67.4%) of the total group of infants developed signs of withdrawal within the first 4 days of life. One hundred seventy-eight or 68.7% of these manifested signs severe enough to require treatment. Eighty-one infants had mild withdrawal signs which cleared without treatment. The 178 treated infants represented 46.3% of the entire group of heroin exposed infants. Our data indicated that there was a direct correlation between the length of maternal addiction and the occurrence of withdrawal signs in the infants; that with an increase of maternal intake of heroin, there was an increased incidence of neonatal withdrawal; and that the closer to delivery the last dose of heroin was taken, the higher and earlier was the occurrence of withdrawal signs in the neonate. Response to treatment with chlorpromazine was excellent. The incidence of congenital anomalies was no higher than in the general newbron population. Morphine and quinine could be demonstrated in the urine of the newborn infants within the first 24 hours of life. Fourteen infants (3.6%) died in the neonatal period; nine of these within the first 9 hours after birth. No evidence of Hyaline Membrane disease was found at autopsy in those that died in respiratory distress.
Human myeloma cell apoptosis induced by interferon‐α (1998)

Although there have been reports regarding the clinical effectiveness of IFN alpha in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy-carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour-cell apoptosis, particularly in immunological prevention. In this study we investigated myeloma cell apoptosis induced by IFN alpha using five human myeloma cell lines which were established without any additional supplementation of IL-6. In addition, the mRNA expression levels of apoptosis-related genes employing the reverse transcriptase-polymerase chain reaction (RT-PCR) were also analysed with the KMS-12-PE cell line, which was the most sensitive of the five cell lines in terms of apoptosis induced by IFN alpha. Based on the results, it was determined that IFN alpha induced myeloma cell apoptosis in a dose-dependent manner, but the sensitivity to IFN alpha in the cell lines examined varied and one cell line revealed growth stimulation by IFN alpha. In addition, the apoptosis induced by IFN alpha did not seem to be mediated by the Fas/Fas ligand pathway. Finally, the IL-6, IL-6R, IRF1 and IRF2 genes were up-regulated in KMS-12-PE cells cultured with IFN alpha. Therefore these genes may play an important role during apoptosis induced by IFN alpha.
An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin (2013)

HER2/HER3 dimerization resulting from overexpression of HER2 or neuregulin (NRG1) in cancer leads to HER3-mediated oncogenic activation of phosphoinositide 3-kinase (PI3K) signaling. Although ligand-blocking HER3 antibodies inhibit NRG1-driven tumor growth, they are ineffective against HER2-driven tumor growth because HER2 activates HER3 in a ligand-independent manner. In this study, we describe a novel HER3 monoclonal antibody (LJM716) that can neutralize multiple modes of HER3 activation, making it a superior candidate for clinical translation as a therapeutic candidate. LJM716 was a potent inhibitor of HER3/AKT phosphorylation and proliferation in HER2-amplified and NRG1-expressing cancer cells, and it displayed single-agent efficacy in tumor xenograft models. Combining LJM716 with agents that target HER2 or EGFR produced synergistic antitumor activity in vitro and in vivo. In particular, combining LJM716 with trastuzumab produced a more potent inhibition of signaling and cell proliferation than trastuzumab/pertuzumab combinations with similar activity in vivo. To elucidate its mechanism of action, we solved the structure of LJM716 bound to HER3, finding that LJM716 bound to an epitope, within domains 2 and 4, that traps HER3 in an inactive conformation. Taken together, our findings establish that LJM716 possesses a novel mechanism of action that, in combination with HER2- or EGFR-targeted agents, may leverage their clinical efficacy in ErbB-driven cancers.
The Information Lens: An Intelligent System for Information Sharing and Coordination (2020)

This chapter describes a prototype system, called the Information Lens, that focuses on one aspect of this problem: how to help people share the many diverse kinds of qualitative information that are communicated via electronic messaging systems. It shows that general capabilities that help with information sharing can be used to support a variety of more specific coordination processes such as task tracking and meeting scheduling. One of the key problems when any group of people cooperates to solve problems or make decisions is how to share information. The Lens system is based on a set of semi-structured messages. For each message type, the system includes a template with a number of fields or slots for holding information. To the construction and use of message templates the templates are arranged in a network so that all subtypes of a given template inherit the field names and property values from the parent template.
Dimethoxypyrimidines as Novel Herbicides. Part 1. Synthesis and Herbicidal Activity of Dimethoxyphenoxyphenoxypyrimidines and Analogues (1996)

A number of 6-(4-phenoxyphenoxy)pyrimidines and triazines were synthesized and their herbicidal activity was measured. Compounds with the methoxy groups at the 2- and 4-positions on the pyrimidine and triazine rings exhibited high herbicidal activity. Introduction of a substituent into the 5-position of the pyrimidine ring diminished the activity. In the phenoxyphenoxy substructure at the 6-position, the central ether bond can be replaced by a methylene group without loss of activity. The optimum substituent on the terminal phenyl ring was 3-trifluoromethyl. The compounds showed a strong Hill reaction inhibition, but unfortunately showed poor selectivity between weeds and crops.
Multidimensional Scaling: History, Theory and Applications. (1988)

Contents: F.W. Young, Part I:History. Introduction. History. F.W. Young, Part II:Theory. Data Theory. Axiomatic Foundations. Unweighted Distance Models. Weighted Distance Models. Part III:Applications. J.A. Cameron, Nuclear Physics: Pattern Recognition in Nuclear Gamma-ray Spectra. L.M. Collins, Sociometry: Deriving Sociograms via Asymmetric Multidimensional Scaling. D.L. Hoffman, W.D. Perreault, Jr., Market Research: Consumer Preference and Perception. D.V. Easterling, Political Science: Using the Generalized Euclidian Model to Study Ideological Shifts in the U.S. Senate. M.R. Jones, R. MacCallum, Psychology: An Application of Principal Directions Scaling to Auditory Pattern Perception. B.H. Forsyth, Psychology: The Subjective Attributes of Natural Categories -- An Application of a Constrained Generalized Euclidian Model.
Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension. (2002)

Rat RGCs subjected to chronic ocular hypertension demonstrate caspase activation and abnormal processing of APP, which may contribute to the pathophysiology of glaucoma.
A Selective ε-Protein Kinase C Antagonist Inhibits Protection of Cardiac Myocytes from Hypoxia-induced Cell Death (1997)

Protein kinase C activation is thought to protect cardiac tissue from subsequent ischemic injury by a process termed preconditioning. The protein kinase C isozyme that mediates preconditioning has not yet been identified. Using a cell culture model of hypoxic preconditioning, we found that cardiac myocyte viability after 9 h of hypoxia was increased by more than 50% over control. Preconditioning activated protein kinase C isozymes as evidenced by translocation from one cell compartment to another as follows: there was a 2.1-fold increase in epsilon-protein kinase C activation, a 2. 8-fold increase in delta-protein kinase C activation, and no increase in betaI-protein kinase C activation. 4beta-Phorbol 12-myristate 13-acetate mimicked hypoxic preconditioning, increasing myocyte survival after prolonged hypoxia by 34% compared with control. We previously identified an epsilon-protein kinase C-selective antagonist, epsilonV1-2 peptide, that inhibits epsilon-protein kinase C translocation and function in cardiac myocytes (Johnson, J. A., Gray, M. O., Chen, C.-H., and Mochly-Rosen, D. (1996) J. Biol. Chem. 271, 24962-24966). epsilonV1-2 peptide abolished hypoxic preconditioning and phorbol ester-mediated cardiac protection. Therefore, preconditioning can be induced in this culture model, and activation of epsilon-protein kinase C is critical for cardiac myocyte protection.
Circulating Irisin in Healthy, Young Individuals: Day-Night Rhythm, Effects of Food Intake and Exercise, and Associations With Gender, Physical Activity, Diet, and Body Composition (2014)

In healthy, young individuals, circulating irisin displays a day-night rhythm, is correlated with lean body mass, and increases acutely after exercise.
Analyzing refractive index changes and differential bending in microcantilever arrays (2008)

A new microcantilever array design is investigated comprising eight flexible microcantilevers introducing two solid bars, enabling to subtract contributions from differences in refractive index in an optical laser read out system. Changes in the refractive index do not contribute undesirably to bending signals at picomolar to micromolar DNA or protein concentrations. However, measurements of samples with high salt concentrations or serum are affected, requiring corrections for refractive index artifacts. Moreover, to obtain a deeper understanding of molecular stress formation, the differential curvature of cantilevers is analyzed by positioning the laser spots along the surface of the levers during pH experiments.
Multilayer Noninteracting Dielectric Metasurfaces for Multiwavelength Metaoptics (2018)

Metasurfaces provide a versatile platform for manipulating the wavefront of light using planar nanostructured surfaces. Transmissive metasurfaces, with full 2π phase control, are a particularly attractive platform for replacing conventional optical elements due to their small footprint and broad functionality. However, the operational bandwidth of metasurfaces has been a critical limitation and is directly connected to either their resonant response or the diffractive dispersion of their lattice. While multiwavelength and continuous band operation have been demonstrated, the elements suffer from either low efficiency, reduced imaging quality, or limited element size. Here, we propose a platform that provides for multiwavelength operation by employing tightly spaced multilayer dielectric metasurfaces. As a proof of concept, we demonstrate a multiwavelength metalens doublet (NA = 0.42) with focusing efficiencies of 38% and 52% at wavelengths of 1180 and 1680 nm, respectively. We further show how this approach can be extended to three-wavelength metalenses as well as a spectral splitter. This approach could find applications in fluorescent microscopy, digital imaging, and color routing.
Immature Dendritic Cells Acquire Cd8+Cytotoxic T Lymphocyte Priming Capacity upon Activation by T Helper Cell–Independent or–Dependent Stimuli (2000)

The well defined, immature murine dendritic cell (DC) line D1 was used to study the role of DC maturation in CTL induction in vitro and in vivo. Maturation of D1 cells, characterized by markedly increased expression of MHC and costimulatory molecules, was induced by incubation with lipopolysaccharide, agonistic CD40 antibody, or specific CD4(+) T helper (Th) cells. Activated, but not immature, D1 cells efficiently primed alloreactive T cell responses in vitro. Similarly, priming of CTL immunity in vivo in CD4-depleted mice was only observed if these mice were immunized with activated D1 cells. This study provides formal evidence that activation of DCs, induced by Th-independent as well as Th-dependent stimuli, is essential for efficient induction of CTL responses.
The Internal Meristem Layer (L3) Determines Floral Meristem Size and Carpel Number in Tomato Periclinal Chimeras (1992)

Eugene J. Szymkowiak, Ian M. Sussex, The Internal Meristem Layer (L3) Determines Floral Meristem Size and Carpel Number in Tomato Periclinal Chimeras, The Plant Cell, Vol. 4, No. 9 (Sep., 1992), pp. 1089-1100
Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. NIAID AIDS Vaccine Clinical Trials Network (1994)

The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response.
ChemInform Abstract: Ligand‐Enabled Methylene C(sp3)—H Bond Activation with a Pd(II) Catalyst. (2013)

Abstract Best results are obtained using 2‐isobutoxyquinoline as the ligand (no stereochemical assignments for most compounds).
Cell death in pancreatitis: Effects of alcohol (2006)

Pancreatitis is a severe and frequently lethal disorder, a major cause of which is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis. In experimental models of (non-alcoholic) acute pancreatitis, acinar cells have been shown to die through both necrosis and apoptosis, the two principal pathways of cell death. The severity of experimental acute pancreatitis correlates directly with the extent of necrosis and inversely with apoptosis. Thus, understanding the regulation of apoptosis and necrosis, and whether it is possible to manipulate the pattern of death responses, is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis. The effects of alcohol on cell death responses of pancreatitis, and the mechanisms that may mediate these effects, are just starting to be explored. This paper reviews the signaling pathways mediating the balance between apoptosis and necrosis in acute pancreatitis, and alcohol's effects on cell death responses in pancreatitis.
Document image decoding using Markov source models (1994)

Document image decoding (DID) is a communication theory approach to document image recognition. In DID, a document recognition problem is viewed as consisting of three elements: an image generator, a noisy channel and an image decoder. A document image generator is a Markov source (stochastic finite-state automaton) that combines a message source with an imager. The message source produces a string of symbols, or text, that contains the information to be transmitted. The imager is modeled as a finite-state transducer that converts the 1D message string into an ideal 2D bitmap. The channel transforms the ideal image into a noisy observed image. The decoder estimates the message, given the observed image, by finding the a posteriori most probable path through the combined source and channel models using a Viterbi-like dynamic programming algorithm. The proposed approach is illustrated on the problem of decoding scanned telephone yellow pages to extract names and numbers from the listings. A finite-state model for yellow page columns was constructed and used to decode a database of scanned column images containing about 1100 individual listings.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice (2008)

4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration of agonistic anti-4-1BB Abs has been previously shown to enhance tumor immunity in mice. Abs are cell-based products posing significant cost, manufacturing, and regulatory challenges. Aptamers are oligonucleotide-based ligands that exhibit specificity and avidity comparable to, or exceeding, that of Abs. To date, various aptamers have been shown to inhibit the function of their cognate target. Here, we have described the development of an aptamer that binds 4-1BB expressed on the surface of activated mouse T cells and shown that multivalent configurations of the aptamer costimulated T cell activation in vitro and mediated tumor rejection in mice. Because aptamers can be chemically synthesized, manufacturing and the regulatory approval process should be substantially simpler and less costly than for Abs. Agonistic aptamers could therefore represent a superior alternative to Abs for the therapeutic manipulation of the immune system.
Thermodynamically Stable Pickering Emulsions (2007)

We show that under appropriate conditions, mixtures of oil, water, and nanoparticles form thermodynamically stable oil-in-water emulsions with monodisperse droplet diameters in the range of 30-150 nm. This observation challenges current wisdom that so-called Pickering emulsions are at most metastable and points to a new class of mesoscopic equilibrium structures. Thermodynamic stability is demonstrated by the spontaneous evolution of binary droplet mixtures towards one intermediate size distribution. Equilibrium interfacial curvature due to an asymmetric charge distribution induced by adsorbed colloids explains the growth of emulsion droplets upon salt addition. Moreover, the existence of a minimal radius of curvature with a concomitant expulsion of excess oil is in close analogy with microemulsions.
Glut-1 Expression Correlates with Basal-like Breast Cancer (2011)

Our results show that Glut-1 is significantly associated with BLBC and might be a potential therapeutic target for this aggressive subgroup of breast cancer, and this warrants further investigations.
Highly Oriented, Self-Assembled Alkanephosphate Monolayers on Tantalum(V) Oxide Surfaces (1999)

Octadecyl phosphoric acid ester has been found to produce oriented, well-ordered monolayers on a flat tantalum(V) oxide surface, via self-assembly from a heptane/propan-2-ol solution. By means of contact angle, optical waveguide lightmode spectroscopy (OWLS), near-edge X-ray absorption fine structure spectroscopy (NEXAFS), and X-ray photoelectron spectroscopy (XPS) measurements, it has been shown that these layers closely resemble those formed by the corresponding thiol−gold system, with respect to packing density, inclination, and order. The system shows promise as an approach to functionalizing oxide surfaces with well-ordered organic monolayers, with potential applications in the fields of biochemical analysis and sensors.
Efficient search using posterior phone probability estimates (2002)

We present a novel, efficient search strategy for large vocabulary continuous speech recognition (LVCSR). The search algorithm, based on stack decoding, uses posterior phone probability estimates to substantially increase its efficiency with minimal effect on accuracy. In particular, the search space is dramatically reduced by phone deactivation pruning where phones with a small local posterior probability are deactivated. This approach is particularly well-suited to hybrid connectionist/hidden Markov model systems because posterior phone probabilities are directly computed by the acoustic model. On large vocabulary tasks, using a trigram language model, this increased the search speed by an order of magnitude, with 2% or less relative search error. Results from a hybrid system are presented using the Wall Street Journal LVCSR database for a 20,000 word task using a backed-off trigram language model. For this task, our single-pass decoder took around 15x realtime on an HP735 workstation. At a cost of 7% relative search error, the decoding time can be speeded up to approximately realtime.