gebhart/patrepeval huggingface dataset:
Convergent Potency of Internalized Gelonin Immunotoxins across Varied Cell Lines, Antigens, and Targeting Moieties (2010)

Gelonin-based immunotoxins vary widely in their cytotoxic potency as a function of antigen density, target cell internalization and trafficking kinetics, and conjugate properties. We have synthesized novel gelonin immunotoxins using two different binding scaffold types (single-chain antibody variable fragments and fibronectin domains) targeting two different tumor antigens (carcinoembryonic antigen and EGF receptor). Constructs were characterized using an antigen-negative cell line (HT-1080), cell lines positive for each antigen (HT-1080(CEA) for carcinoembryonic antigen and A431 for EGF receptor), and a cell line positive for both antigens (HT-29). Immunotoxins exhibited K(d) values between 8 and 15 nm and showed 20-2000-fold enhanced cytotoxicity compared with gelonin (IC(50) ∼ 0.25-30 nM versus 500 nM). Using quantitative fluorescence flow cytometry, we measured internalization of gelonin (via pinocytosis) and gelonin-based immunotoxins (via antigen-dependent, receptor-mediated endocytosis). Results were matched with cytotoxicity measurements made at equivalent concentration and exposures. Unexpectedly, when matched internalization and cytotoxicity data were combined, a conserved internalized cytotoxicity curve was generated that was common across experimental conditions. Considerable variations in antigen expression, trafficking kinetics, extracellular immunotoxin concentration, and exposure time were all found to collapse to a single potency curve on the basis of internalized immunotoxin. Fifty percent cytotoxicity occurred when ∼ 5 × 10(6) toxin molecules were internalized regardless of the mechanism of uptake. Cytotoxicity observed at a threshold internalization was consistent with the hypothesis that endosomal escape is a common, highly inefficient, rate-limiting step following internalization by any means tested. Methods designed to enhance endosomal escape might be utilized to improve the potency of gelonin-based immunotoxins.
The Level of Virus-Specific T-Cell and Macrophage Recruitment in Porcine Reproductive and Respiratory Syndrome Virus Infection in Pigs Is Independent of Virus Load (2004)

Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important infectious disease agent of pigs worldwide, causing reproductive failure in pregnant sows and respiratory problems in nursing and growing pigs. PRRSV infection is characterized by a prolonged viremia of 30 or more days and an extended persistent infection of lymphoid tissues. To better understand the immunological basis for prolonged acute and persistent PRRSV infection, we have examined the cell-mediated immune (CMI) response throughout the course of infection and compared the results to the local distribution and abundance of PRRSV in infected tissues. PRRSV-specific T cells, enumerated by gamma interferon enzyme-linked immunospot assay, did not appear until 2 weeks after PRRSV inoculation, and their abundance exhibited substantial variation over time and among animals. In all cases the T-cell response was transient. High levels of viral RNA were present in lymphoid tissues of all animals in the acute phase of infection. Viral loads were decreased 1,000-fold or more in persistent infections, with the primary sites of persistence being tonsil, sternal lymph node, and inguinal lymph node. The abundance of virus-specific T cells in either acutely or persistently infected animals was highly variable and showed no correlation to the level of virus in lymphoid tissues. No significant difference in antigen-specific T-cell abundance was observed in secondary lymphoid tissues in either acute or persistent infection except for tonsil, in which the number of responding cells was extremely low. CD4(+)- and CD8(+)-T-cell frequencies did not change after PRRSV infection, though a decrease in gammadelta T cells was observed. Macrophages, the permissive cell type for PRRSV, were present in various levels in all tissue preparations and were not in proportion to local virus load. These findings indicate that a weak CMI response contributes to prolonged PRRSV infection and suggests that PRRSV suppresses T-cell recognition of infected macrophages. Thus, the slow but eventual resolution of PRRSV infection may be dependent on limiting permissive macrophages and on innate immune factors.
Optknock: A bilevel programming framework for identifying gene knockout strategies for microbial strain optimization (2003)

The advent of genome-scale models of metabolism has laid the foundation for the development of computational procedures for suggesting genetic manipulations that lead to overproduction. In this work, the computational OptKnock framework is introduced for suggesting gene deletion strategies leading to the overproduction of chemicals or biochemicals in E. coli. This is accomplished by ensuring that a drain towards growth resources (i.e., carbon, redox potential, and energy) must be accompanied, due to stoichiometry, by the production of a desired product. Computational results for gene deletions for succinate, lactate, and 1,3-propanediol (PDO) production are in good agreement with mutant strains published in the literature. While some of the suggested deletion strategies are straightforward and involve eliminating competing reaction pathways, many others suggest complex and nonintuitive mechanisms of compensating for the removed functionalities. Finally, the OptKnock procedure, by coupling biomass formation with chemical production, hints at a growth selection/adaptation system for indirectly evolving overproducing mutants.
Free energy calculations for theophylline binding to an RNA aptamer: Comparison of MM‐PBSA and thermodynamic integration methods (2002)

Abstract We have applied the molecular mechanics Poisson–Boltzmann surface area (MM‐PBSA) method (J. Srinivasan, T. E. Cheatham, P. Cieplak, P. A. Kollman, and D. A. Case, Journal of the American Chemical Society , 1998, Vol. 120, pp. 9401–9409) to study the interaction of an RNA aptamer with theophylline and its analogs. The MM‐PBSA free energy analysis provides a reasonable absolute binding free energy for the RNA aptamer–theophylline complex formation. Energetic analysis reveals that the van der Waals interaction and the nonpolar contribution to solvation provide the basis for the favorable absolute free energy of complex. This trend is similar to other protein–ligand interactions studied previously. The MM‐PBSA method also ranks the relative binding energies of five theophylline analogs approximately correctly, but not as well as the more conventional thermodynamic integration calculations, which were carried out to convert theophylline into its analogs. The comparison of MM‐PBSA with TI suggests that the MM‐PBSA method has some difficulties with the first‐solvation‐shell energetics. © 2002 Wiley Periodicals, Inc. Biopolymers 68: 16–34, 2003
NiCr Alloy As Both Absorption Layer and Top Electrode onto Pb(Zr0.3Ti0.7)O3 Thin Films for Infrared Sensors (2003)

NiCr alloys prepared by dc magnetron sputtering are considered to apply simultaneously both the absorption layer and the top electrode on PZT thin films for infrared sensors. NiCr alloys deposited with dc powers of Ni 80 and Cr 50 W showed the most stable oxidation resistance even at 600°C in an oxygen ambient. They have a resistivity of approximately 70 μΩ-cm and a rms roughness of 2.0 nm in samples annealed at 600°C for 5 min in O2. The NiCr/PZT/Pt capacitors showed a well-saturated hysteresis loop having a remanent polarization of 20 μC/cm2. Ultra-thin NiCr alloys showed a possibility as a top electrode for infrared sensors.
Transient thermoreflectance from thin metal films (1985)

New exotic materials such as amorphous alloys and superlattices are often deposited as thin films onto substrates thereby complicating conventional thermal transport measurements. Transient thermoreflectance (TTR) allows measurements on thin films by the generation of ultrafast heating and time-resolved measurements of the thermally induced reflectivity change on a picosecond time scale. Typically, the penetration depth of visible light in a metal is ~20 nm, and thermal diffusion out of this region occurs in a few hundred picoseconds. Therefore, for film thicknesses of ~100 nm or greater, the TTR measurement can be completed before substrate effects become important. Since the heating depth is small compared to the diameter of the illuminated surface, a 1-D heat flow model can be fitted to our measurements with the thermal diffusivity as a free parameter. We have made TTR measurements on sputtered and evaporated nickel, iron, and zirconium films with thickness between 100 and 500 nm. Deposition-induced disorder decreases the thermal diffusivity of the Fe and Ni, in agreement with electrical conductivity measurements. The Zr film exhibits anomalous behavior possibly indicative of a breakdown in the Wiedemann-Franz law. The extension of this technique to composite films is also discussed.
Fabrication of optical fibres containing low levels of rare-earth ions (1985)

Fibres containing rare-earths have been produced with high absorption levels in the visible and near infra-red regions. This has been achieved without significantly compromising the low-loss characteristics at wavelengths between 900 and 1400 nm.
Chemoselective fragment condensation between peptide and peptidomimetic oligomers (2013)

We report the first example of chemoselective fragment condensation, through native amide bond formation, between peptoid and peptide oligomers. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to peptides containing N-terminal serine or threonine residues. We investigate the ligation efficiency of peptoid oligomers varying in length, sequence, and C-terminal steric bulk. These protocols enhance accessibility of structurally complex peptoid-peptide hybrids and will facilitate the design new semi-synthetic proteins with unique attributes.
COMPARATIVE HEMODYNAMIC, METABOLIC AND HORMONAL EFFECTS OF HYPOTENSION INDUCED WITH ATP AND NITROPRUSSIDE (1982)

Department of Anesthesiology, Harbor/UCLA Medical Center, 1000 W. Carson ST., Torrance, Ca., 90509, and Department of Anesthesiology, University of California Los Angeles. School of Medicine, Center for the Health Sciences, Los Angeles, CA, 90024
Selective Activation of A3Adenosine Receptors WithN6-(3-Iodobenzyl)Adenosine-5′-N-Methyluronamide Protects Against Myocardial Stunning and Infarction Without Hemodynamic Changes in Conscious Rabbits (1997)

To examine the cardioprotective role of A3 adenosine receptors during myocardial ischemia/reperfusion injury, we tested the effect of N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), a potent and selective A3 adenosine receptor agonist, in models of myocardial stunning and infarction in chronically instrumented conscious rabbits. In phase I (studies of myocardial stunning), rabbits were subjected to six 4-minute coronary occlusions, each separated by 4-minute reperfusion periods, after which the recovery of systolic wall thickening was measured (ultrasonic crystals). In phase II (studies of myocardial infarction), rabbits were subjected to a 30-minute coronary occlusion followed by 3 days of reperfusion. In both phases, IB-MECA was administered as an intravenous bolus (100 micrograms/kg) 10 minutes before the first coronary occlusion. This dose of IB-MECA was determined in pilot studies to have no effect on heart rate, arterial blood pressure, or plasma histamine concentration in rabbits. In phase I, IB-MECA markedly improved the recovery of wall thickening after the six occlusion/reperfusion cycles, and this effect was sustained throughout the 5-hour observation period; the total deficit of wall thickening (a measure of the overall severity of myocardial stunning) was reduced by 68% (control, 129 +/- 16 arbitrary units, n = 7; IB-MECA, 41 +/- 6 arbitrary units, n = 6; P < .01). The protective effects of IB-MECA against stunning were completely blocked by pretreatment with the nonselective adenosine receptor antagonist 8-p-sulfophenyl theophylline or the specific protein kinase C inhibitor chelerythrine. In phase II, IB-MECA reduced myocardial infarct size by 61%; infarct size (tetrazolium staining) was 41 +/- 4% of the risk region in control animals (n = 8) and 16 +/- 6% in IB-MECA-treated animals (n = 8, P < .01). These results demonstrate that in conscious rabbits the A3 adenosine receptor agonist IB-MECA confers a powerful protection against both reversible (stunning) and irreversible (infarction) injury during acute myocardial ischemia and reperfusion by a protein kinase C-mediated pathway, suggesting that selective activation of A3 receptors is an effective means of protecting the ischemic myocardium without hemodynamic changes.
On the Use of the Dual Process Langmuir Model for Predicting Unary and Binary Isosteric Heats of Adsorption (2012)

Analytic expressions for unary and binary isosteric heats of adsorption as a function of the adsorbed phase loading were derived from the dual process Langmuir (DPL) model using the Clausius-Clapeyron equation. Unary isosteric heats of adsorption predicted from these expressions for several adsorbate-adsorbent systems were compared to values in the literature predicted from the well-accepted graphical approach using Toth and unilan models (Adsorption Equilibrium Data Handbook; Prentice Hall: NJ, 1989). Predictions from the DPL model were also compared to rare experimental unary and binary isosteric heats of adsorption in the literature for another adsorbate-adsorbent system. In all cases, very good agreement was obtained, showing that the DPL model can be used in adsorption process modeling for accurately predicting not only ideal and nonideal mixed-gas adsorption equilibria (Langmuir 2011, 27, 4700), but also unary and even binary isosteric heats of adsorption.
Medicinal Chemistry of hERG Optimizations: Highlights and Hang‐Ups (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Amelioration of infant sleep disturbances: II. Effects of scheduled awakenings by compliant parents (1985)

Twelve infants and toddlers who exhibited spontaneous awakening and crying episodes during the night were subjected to scheduled awakenings by their parents. Scheduled awakenings were determined from individual baseline data, and these consisted of awakening, feeding, and consoling the child about 15 to 30 minutes before typical spontaneous awakening times. Once spontaneous awakenings were precluded, scheduled awakenings by the parents were faded out and posttreatment data were collected. The technique appeared effective for most children when the parents complied with the procedure.
Stimulated emission at 474nm from an InGaN laser diode structure grown on a (112¯2) GaN substrate (2007)

The stimulated emissions from semipolar InGaN laser diode (LD) structures grown on (112¯2) GaN substrates are observed at room temperature under photopumped conditions. The measured emission peaks are in the photon energy range from 2.62eV (474nm)to3.05eV (405nm), and the emission intensity has a threshold behavior with respect to the pumping power. A strong in-plane optical anisotropy is observed between the two perpendicular directions, [1¯1¯23] and [11¯00], due to anisotropic matrix elements, which depend on the crystal orientation; the stimulated emission measured along the [1¯1¯23] direction occurs with a lower threshold pumping power at a lower energy compared to that obtained along the [11¯00] direction. The experimental results and the valence band calculations indicate that the transverse-electric mode with an electric vector along the [11¯00] direction is dominant for gain formation in semipolar and nonpolar InGaN LDs. Compared to c-plane InGaN LDs, semipolar InGaN LDs have comparable or less threshold pumping powers.
A 512kB Embedded Phase Change Memory with 416kB/s Write Throughput at 100&#x003BC;A Cell Write Current (2007)

An experimental 512kB embedded PCM uses a current-saving architecture in a 0.13μm 1.5V CMOS. The write scheme features a low-write-current resistive device and achieves 416kB/s write-throughput at 100muA cell current. A charge-transfer direct-sense scheme has a 16b parallel read access time of 9.9ns in an array drawing 280μA. A standby voltage scheme suppresses leakage current in the cell current path and increases the measured PCM cell resistance from 3 to 33MΩ.
Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin (2008)

Hemojuvelin (HJV) is a coreceptor for bone morphogenetic protein (BMP) signaling that regulates hepcidin expression and iron metabolism. However, the precise combinations of BMP ligands and receptors used by HJV remain unknown. HJV has also been demonstrated to bind to neogenin, but it is not known whether this interaction has a role in regulating hepcidin expression. In the present study, we show that BMP-2, BMP-4, and BMP-6 are endogenous ligands for HJV in hepatoma-derived cell lines, and that all 3 of these ligands are expressed in human liver. We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. Interestingly, ActRIIA is the predominant BMP type II receptor expressed in human liver. While HJV can use all 3 BMP type I receptors (ALK2, ALK3, and ALK6) in vitro, only ALK2 and ALK3 are detected in human liver. Finally, we show that HJV-induced BMP signaling and hepcidin expression are not altered by neogenin overexpression or by inhibition of endogenous neogenin expression. Thus, HJV-mediated BMP signaling and hepcidin regulation occur via a distinct subset of BMP ligands and BMP receptors, independently of neogenin.
STAT3 Regulates the Generation of Th17 Cells (2007)

CD4 + helper T (Th) cells that produce interleukin-17 (IL-17) are a distinct lineage of Th cells (Th17 cells) and are important in autoimmune disorders. Exactly how cytokine signaling generates Th17 cells is only recently becoming clear. IL-6 stimulates Th17 differentiation in vitro, so Yang et al . analyzed splenocytes from immunized wild-type and Il-6 knockout mice by flow cytometry and found that Il-6 knockout mice had the fewest Th17 cells. Interferon-γ (IFN-γ) inhibits Th17 differentiation, so naïve T cells from IFN-γ-deficient mice were activated in vitro with anti-CD3 and anti-CD28 in the presence or absence of cytokines and/or cytokine-neutralizing antibodies. IL-6 simulated production of Th17 cells, whereas IL-23 resulted in few Th17 cells but synergized with IL-6. This effect might be due to the increased amounts of IL-23 receptor (IL-23R) mRNA observed in IL-6-treated naïve CD4 + T cells, as measured by real-time polymerase chain reaction. Infection of naïve CD4 + T cells from IFN-γ-deficient mice with a retrovirus encoding a hyperactive form of signal transducer and activator of transcription-3 (STAT3) resulted in more Th-17 cells and higher amounts of mRNAs for IL-17 and IL-22 than in control cells. Activation of naïve CD4 + T cells from mice with a hematopoietic-specific deletion of Stat3 produced fewer Th17 cells and lower amounts of IL-17 and IL-22 mRNAs than did equivalent treatment of wild-type cells. Activated CD4 + T cells from Stat3 knockout mice had lower amounts of mRNAs for IL-23R and RORγt (retinoic acid receptor-related orphan receptor γ-T), a Th17-specific transcription factor. This study nominates STAT3 as the essential regulator of Th17 cells, analogous to STAT4 and STAT1 in Th1 cells and STAT6 in Th2 cells. X. O. Yang, A. D. Panopoulos, R. Nurieva, S. H. Chang, D. Wang, S. S. Watowich, C. Dong, STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem. 282 , 9358-9363 (2007). [Abstract] [Full Text]
FBC's Potential of 6F2 Single Cell Operation in Multi-Gbit Memories Confirmed by a Newly Developed Method for Measuring Signal Sense Margin (2007)

A 6F <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> single cell (one-cell-per-bit) operation of the floating body RAM (FBRAM) is successfully demonstrated for the first time with more than 60% yield of 16Mbit area in a wafer. The signal sense margin (SSM) at actual read conditions is found to well back up the functional results. The parasitic resistance in the source and drain formed under the FBC's spacers can be optimized for making the SSM as large as 8muA at plusmn 4.5sigma without sacrificing the retention time.
Internal Antenna Design for a Triple Band Using an Overlap of Return Loss (2007)

A design scheme of a triple band internal antenna is proposed for use in GSM900, DCS1800, and PCS1900 bands. The folding metal plates of the two branches are mounted on a dielectric-coated ground plane for size miniaturization and durability. For a wide-band operation, the return loss overlapping method is used by controlling the length of the metal branches. The return loss of the suggested antenna geometry was calculated by a commercial HFSS 9 simulator and the results are compared with measured return loss, which shows a good agreement between them. Gain and radiation pattern are also measured by the field measurement system in an anechoic chamber.
Administration of a highly attenuated, live respiratory syncytial virus vaccine to adults and children (1982)

A highly attenuated respiratory syncytial virus (RSV) experimental vaccine, RSV ts-2, was sequentially evaluated in adults, seropositive children, and finally, fully susceptible seronegative children. The vaccine was administered intranasally in doses ranging from 10(5.2) to 10(6.3) PFU/ml. In both adults and children, the vaccine proved to be poorly infectious. Although poor infectivity would not have been predicted from tissue culture studies of RSV ts-2 growth, the human experience closely parallels the experience in a series of animal models, including the chimpanzee. The poor infectivity of this RSV vaccine virus preparation suggests that the postulated defect in the RSV ts-2 fusion protein may be important in determining in vivo infectivity of RSV.
The first synthesis of a fully functionalized core structure of staurosporine: sequential indolyl glycosidation by endo and exo glycals (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe first synthesis of a fully functionalized core structure of staurosporine: sequential indolyl glycosidation by endo and exo glycalsJ. T. Link, Michel Gallant, Samuel J. Danishefsky, and Susan HuberCite this: J. Am. Chem. Soc. 1993, 115, 9, 3782–3783Publication Date (Print):May 1, 1993Publication History Published online1 May 2002Published inissue 1 May 1993https://pubs.acs.org/doi/10.1021/ja00062a057https://doi.org/10.1021/ja00062a057research-articleACS PublicationsRequest reuse permissionsArticle Views409Altmetric-Citations51LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts