gebhart/patrepeval huggingface dataset:
A study of monoclonal antibody‐producing CHO cell lines: What makes a stable high producer? (2008)

Generating stable, high-producing cell lines for recombinant protein production requires an understanding of the potential limitations in the cellular machinery for protein expression. In order to increase our understanding of what makes a stable high producer, we have generated a panel of 17 recombinant monoclonal antibody expressing Chinese hamster ovary subclones (CHO-mAb) with specific productivities ranging between 3 and 75 pg cell(-1) day(-1) using the dihydrofolate reductase (dhfr) expression system and compared the molecular features of these high- and low-producer clones. The relative heavy chain (HC) and light chain (LC) transgene copy numbers and mRNA levels were determined using real-time quantitative PCR (RT qPCR). We observed that not only higher transgene copy numbers and mRNA levels of both HC and LC were characteristic for the high-producer clones as compared to the low-producer clones but also a more favorable HC to LC transgene copy numbers ratio. By studying the long-term stability of the CHO-mAb subclones in the absence of methotrexate (MTX) selective pressure over 36 passages we observed a 35-92% decrease in volumetric productivity, primarily caused by a significant decrease in HC and LC mRNA levels with little change in the transgene copy numbers. Using Southern blot hybridization we analyzed the HC and LC transgene integration patterns in the host chromosome and their changes in course of gene amplification and long-term culturing. We observed that MTX-induced gene amplification caused chromosomal rearrangements resulting in clonal variability in regards to growth, productivity, and stability. No further obvious DNA rearrangements occurred during long-term culturing in the absence of MTX, indicating that other mechanisms were responsible for the decreased transcription efficiency. Our results implicate that the amplified transgene sequences were arranged in tandem repeats potentially triggering repeat-induced gene silencing. We hypothesize that the decline in transgene mRNA levels upon long-term culturing without MTX was mainly caused by transgene silencing consequently leading to a loss in mAb productivity. The exact molecular mechanisms causing production instability are not yet fully understood. The herein described extensive characterization studies could help understand the limitations to high-level, stable recombinant protein production and find ways to improving and accelerating the process for high-producer cell line generation and selection.
Serial Pronuclear Transfer Increases the Developmental Potential of In Vitro-Matured Oocytes in Mouse Cloning1 (2002)

In vitro-matured germinal vesicle oocytes are an interesting source of cytoplast recipients in both animal and human nuclear transfer (NT) experiments. We investigated two technical aspects that might improve the developmental potential of nuclear transfer mouse embryos constructed from in vitro-matured germinal vesicle oocytes. In a first step, the effect of two maturation media on the embryonic development of NT embryos originating from in vitro-matured oocytes was compared. Supplementation of the oocyte maturation medium with serum and gonadotrophins improved the developmental rate of NT embryos constructed from in vitro-matured oocytes, but it was still inferior to that obtained with in vivo-matured metaphase II (MII) oocytes. Second, we investigated the effect of serial pronuclear transfer from NT zygotes originating from both in vitro- and in vivo-matured oocytes to in vivo-fertilized zygotic cytoplasts. Blastocyst quality was evaluated by counting nuclei from trophectoderm and inner cell mass cells using a differential staining. Sequential pronuclear transfer significantly improved the blastocyst formation rate of NT embryos originating from in vitro-matured oocytes up to the rate obtained with in vivo-matured MII oocytes. We conclude that the developmental potential of NT embryos constructed from in vitro-matured oocytes can be optimized by serial pronuclear transfer to in vivo-produced zygotic cytoplasts.
Intraoperative Fluorescence Imaging of Peripheral and Central Nerves Through a Myelin-Selective Contrast Agent (2012)

Fluorescence imaging of nerves through myelin showed a potential for use in image-guided surgery. Intraoperative nerve imaging is an example where contrast agent and instrument development come together as a result of clinical need.
Red, Green, and Blue Colors in Polymeric Electrochromics (2004)

Additive primary color-space has been completed by the discovery of the first green polymeric electrochromic. Mixing any two of the three additive primary colors (red, green, and blue (RGB)) produces thousands of colors (see Figure) resulting from the tones of polymers in different oxidation states. It is envisioned that the completion of the three components of color-space and the discovery of the first green polymeric electrochromic will herald a new polymeric electrochromic device era.
Modulation of Renal Disease in MRL/lpr Mice by Suberoylanilide Hydroxamic Acid (2004)

Epigenetic regulation of gene expression is involved in the development of many diseases. Histone acetylation is a posttranslational modification of the nucleosomal histone tails that is regulated by the balance of histone deacetylases and histone acetyltransferases. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are a hallmark of many diseases, including systemic lupus erythematosus. In this study, we determined whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor: 1) inhibits inflammatory mediator production in vitro and 2) modulates lupus progression in vivo. Mesangial cells isolated from 10-wk-old MRL/lpr mice were stimulated with LPS/IFN-gamma and incubated with SAHA. TNF-alpha, IL-6, NO, and inducible NO synthase expression were inhibited by SAHA. We then treated MRL/lpr mice with daily injections of SAHA from age 10 to 20 wk. The animals treated with SAHA had decreased spleen size and a concomitant decrease in CD4-CD8- (double-negative) T cells compared with controls. Serum autoantibody levels and glomerular IgG and C3 deposition in SAHA-treated mice were similar to controls. In contrast, proteinuria and pathologic renal disease were significantly inhibited in the mice receiving SAHA. These data indicate that SAHA blocks mesangial cell inflammatory mediator production in vitro and disease progression in vivo in MRL/lpr mice.
Structure and Properties of a Dimeric N-terminal Fragment of Human Ubiquitin (2002)

Previous peptide dissection and kinetic experiments have indicated that in vitro folding of ubiquitin may proceed via transient species in which native-like structure has been acquired in the first 45 residues. A peptide fragment, UQ(1-51), encompassing residues 1 to 51 of ubiquitin was produced in order to test whether this portion has propensity for independent self-assembly. Surprisingly, the construct formed a folded symmetrical dimer that was stabilised by 0.8 M sodium sulphate at 298 K (the S state). The solution structure of the UQ(1-51) dimer was determined by multinuclear NMR spectroscopy. Each subunit of UQ(1-51) consists of an N-terminal β-hairpin followed by an α-helix and a final β-strand, with orientations similar to intact ubiquitin. The dimer is formed by the third β-strand of one subunit interleaving between the hairpin and third strand of the other to give a six-stranded β-sheet, with the two α-helices sitting on top. The helix-helix and strand portions of the dimer interface also mimic related features in the structure of ubiquitin. The structural specificity of the UQ(1-51) peptide is tuneable: as the concentration of sodium sulphate is decreased, near-native alternative conformations are populated in slow chemical exchange. Magnetization transfer experiments were performed to characterize the various species present in 0.35 M sodium sulphate, namely the S state and two minor forms. Chemical shift differences suggest that one minor form is very similar to the S state, while the other experiences a significant conformational change in the third strand. A segmental rearrangement of the third strand in one subunit of the S state would render the dimer asymmetric, accounting for most of our results. Similar small-scale transitions in proteins are often invoked to explain solvent exchange at backbone amide proton sites that have an intermediate level of protection.
Hairy cell leukemia: an interferon deficient disease? (1985)

rIFN-alpha 2 is an effective substance in the treatment of HCL. Although the complete eradication of hairy cells from the bone marrow is rarely possible, a dramatic improvement of profound cytopenias can be obtained in most patients, 12 out of 13 in this study. The response can be seen after a median treatment duration of about 2 months and appears to be independent of the presence of the spleen. Once a stable improvement of the peripheral blood values is achieved, one dose of rIFN-alpha 2 every other week may be sufficient to maintain the cell counts. The mechanism(s) by which IFN acts remain unclear. We speculate, that HCL is an IFN deficient syndrome because monocytes which are the major source of IFN-alpha are severely depressed in this lymphoproliferative disorder. Following this hypothesis, the IFN therapy would be comparable to the substitution of insulin in diabetic patients.
Neutrophil-Gelatinase-Associated Lipocalin and Renal Function after Percutaneous Coronary Interventions (2006)

NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine, duration of PCI, but not type and amount of contrast agent, and appropriate treatment of diabetes, reflected by HbA1c, predict a rise in serum NGAL and kidney function following PCI.
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma (2010)

Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
Transferred substrate Schottky-collector heterojunction bipolar transistors: first results and scaling laws for high f/sub max/ (1995)

Unlike normal heterojunction bipolar transistors (HBT's), transferred substrate Schottky-collector HBT's (SCHBT's) exhibit substantial increases in f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> as the emitter and collector stripes are scaled to deep submicron dimensions. First generation InAlAs/InGaAs SCHBT's with aligned 1-μm emitter and collector stripes have been fabricated.
All-D-Enantiomers of β-Amyloid Exhibit Similar Biological Properties to All-L-β-Amyloids (1997)

The amyloidogenic peptide beta-amyloid has previously been shown to bind to neurons in the form of fibrillar clusters on the cell surface, which induces neurodegeneration and activates a program of cell death characteristic of apoptosis. To further investigate the mechanism of Abeta neurotoxicity, we synthesized the all-D- and all-L-stereoisomers of the neurotoxic truncated form of Abeta (Abeta25-35) and the full-length peptide (Abeta1-42) and compared their physical and biological properties. We report that the purified peptides exhibit nearly identical structural and assembly characteristics as assessed by high performance liquid chromatography, electron microscopy, circular dichroism, and sedimentation analysis. In addition, both enantiomers induce similar levels of toxicity in cultured hippocampal neurons. These data suggest that the neurotoxic actions of Abeta result not from stereoisomer-specific ligand-receptor interactions but rather from Abeta cellular interactions in which fibril features of the amyloidogenic peptide are a critical feature. The promiscuous nature of these beta-sheet-containing fibrils suggests that the accumulation of amyloidogenic peptides in vivo as extracellular deposits represents a site of bioactive peptides with the ability to provide inappropriate signals to cells leading to cellular degeneration and disease.
Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis (2006)

Pattern-recognition receptors (PRRs) trigger innate immune responses in animals and plants. One such PRR is the flagellin receptor FLS2 in Arabidopsis. Here, we demonstrate that a functional fusion of FLS2 to the green fluorescent protein (GFP) resides in cell membranes of most tissues. Stimulation with the flagellin epitope flg22 induces its transfer into intracellular mobile vesicles, followed by degradation. FLS2 internalization depends on cytoskeleton and proteasome functions, and receptor activation. A variant FLS2 mutated in Thr 867, a potential phosphorylation site, binds flg22 normally, but is impaired in flg22 responses and FLS2 endocytosis. We propose that plant cells regulate pathogen-associated molecular pattern (PAMP)-mediated PRR activities by subcellular compartmentalization.
Cycloadditions of Nonstabilized 2‐Azaallyllithiums (2‐Azaallyl Anions) and Azomethine Ylides with Alkenes: [3 + 2] Approaches to Pyrrolidines and Application to Alkaloid Total Synthesis. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Resistance to Tracking and Erosion of Silicone Rubber Material under Various Types of Precipitation (1999)

Environment stress and contaminants have become more and more severe due to the development of industry. Outdoor polymer insulating materials in use may suffer from rainwater containing various chemical contaminants so that their resistance to tracking degrades. In this paper, the tracking resistance of high-temperature vulcanized silicone rubber (HTVSR) under various types of precipitation is evaluated by the incline-plane method, using artificial rainwater as a contaminant. The influences of ion concentration, acidity, and conductivity of rainwater on the energized silicone rubber material are studied. Experimental results reported here show that the degradation of the energized material increases with the ion concentration of the rainwater; the discharge current and the erosion of material increase. The conductive ions in rainwater could induce more tracking and discharge on the energized material surface, and acidic rainwater could accelerate the electrolyte process in the materials and dissolve the inorganic filler in silicone rubber. Although silicone rubber degrades under our process of accelerated aging using artificial rainwater, the ion concentration, acidity and conductivity of actual precipitation is insufficient to exert a significant degradation effect on silicone rubber. Silicone rubber can resist the erosion of even the most corrosive rainwater and does not fail.
Characterization and estimation of barley polysaccharides by near-infrared spectroscopy. I. Barleys, starches, and beta-D-glucans (1992)

The objective was to determine whether NIRS can be used to estimate the total β-glucan content of barley. To this end, first were determined factos that govern and affect the NIRS assay. Thode factors included naked versus covered barleys, small and large starch granules, and starches isolated from barley that varied in amylose content
NUMERICAL AND EXPERIMENTAL STUDY OF FLOW AND HEAT TRANSFER IN OUTWARDLY CONVEX CORRUGATED TUBES WITH A TWISTED TAPE INSERT (2018)

This study involves numerical and experimental investigations on flow and heat transfer in an outwardly convex corrugated tube with various structural twisted tape inserts (CT) by using computational fluid dynamics (CFD) methods. The numerical mode is validated by comparing it with experimental data for a smooth tube and corrugated tubes in a developed experimental apparatus. The study also includes a comparison of thermodynamic performances of a CT, a smooth tube with a twisted tape insert (ST), and of a smooth tube to determine their differences. The influence of a twist ratio is considered to analyze thermodynamic regulation and reveal the mechanism operating in CT. The numerical results also agree well with the experimental results on the Nusselt number and friction factor of the corrugated and smooth tubes. The maximum deviations are controlled within ± 6% for Nuc and ± 7.6% for fc. The Nu in the CT exceeds those in the ST and smooth tube by 120-136% and 171-317%, respectively. The friction factor in the CT exceeds those in the ST and plain tube by 148-153% and 476-514%, respectively. The effect of twist ratio in a CT is considered, and the results indicate that the best overall thermal performance (η = 1.97) is obtained with a high twist ratio (y/w = 5). However, the highest thermal performance (Nuc/Nus = 4.78) is obtained with the lowest twist ratio (y/w = 1.25). The contour plots indicate that a potential reason for this can be attributed to the coexistence of the corrugated tubes and tapes that provide a synergetic swirling effect, which efficiently reduces the thermal and velocity boundary layer developments and thus effectively increases the heat transfer performance.
Database of Genomic Biomarkers for Cancer Drugs and Clinical Targetability in Solid Tumors (2015)

Comprehensive genomic profiling is expected to revolutionize cancer therapy. In this Prospective, we present the prevalence of mutations and copy-number alterations with predictive associations across solid tumors at different levels of stringency for gene-drug targetability. More than 90% of The Cancer Genome Atlas samples have potentially targetable alterations, the majority with multiple events, illustrating the challenges for treatment prioritization given the complexity of the genomic landscape. Nearly 80% of the variants in rarely mutated oncogenes are of uncertain functional significance, reflecting the gap in our understanding of the relevance of many alterations potentially linked to therapeutic actions. Access to targeted agents in early clinical trials could affect treatment decision in 75% of patients with cancer. Prospective implementation of large-scale molecular profiling and standardized reports of predictive biomarkers are fundamental steps for making precision cancer medicine a reality.
Regulation of the ras signalling network (1994)

The mitogenic action of cytokines such as epidermal growth factor (EGF) or platelet derived growth factor (PDGF) involves the stimulation of a signal cascade controlled by a small G protein called Ras. Mutations of Ras can cause its constitutive activation and, as a consequence, bypass the regulation of cell growth by cytokines. Both growth factor-induced and oncogenic activation of Ras involve the conversion of Ras from the GDP-bound (D-Ras) to the GTP-bound (T-Ras) forms. T-Ras activates a network of protein kinases including c-Mos, c-Raf-1 and MAP kinase. Eventually the activation of MAP kinase leads to the activation of the elongation factor 4E and several transcription factors such as c-Jun, c-Myc and c-Fos. There are several modulators of Ras activity, such as the GTPase activating proteins (GAP1 and NF1), which stimulate the conversion of T-Ras to D-Ras. A series of small NF1 fragments, which bind T-Ras, as well as truncated forms of derivatives of c-Raf-1, c-Jun and c-Myc, are capable of blocking the T-Ras-activated mitogenesis in a competitive manner. These agents offer a unique opportunity to control the proliferation of T-Ras-associated tumors, which represent more than 30% of total human carcinomas.
The close homologue of the neural adhesion molecule L1 (CHL1): patterns of expression and promotion of neurite outgrowth by heterophilic interactions (1999)

The close homologue of L1 (CHL1), a member of the L1 family of neural adhesion molecules, is first expressed at times of neurite outgrowth during brain development, and is detectable in subpopulations of neurons, astrocytes, oligodendrocyte precursors and Schwann cells of the mouse and rat. Aggregation assays with CHL1-transfected cells show that CHL1 does not promote homophilic adhesion or does it mediate heterophilic adhesion with L1. CHL1 promotes neurite outgrowth by hippocampal and small cerebellar neurons in substrate-bound and soluble form. The observation that CHL1 and L1 show overlapping, but also distinct patterns of synthesis in neurons and glia, suggests differential effects of L1-like molecules on neurite outgrowth.
RIG-I-Mediated STING Upregulation Restricts Herpes Simplex Virus 1 Infection (2016)

The innate immune system represents the first line of defense against invading pathogens. The dysregulation of this system can result in failure to combat pathogens, inflammation, and autoimmune diseases. Thus, precise regulation at each level of the innate immune system is crucial. Recently, a number of studies have established STING to be a central molecule in the innate immune response to cytosolic DNA and RNA derived from pathogens. Here, we describe the regulation of STING via RIG-I-mediated innate immune sensing. We found that STING is synergistically induced via proinflammatory and antiviral cytokine cascades. In addition, we show that in vivo protection against herpes simplex virus 1 (HSV-1) by a RIG-I agonist required STING. Our study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING.
Naphthoquinone Antimalarials. XIV. 2-Hydroxy-3-aryl-1,4-naphthoquinones (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNaphthoquinone Antimalarials. XIV. 2-Hydroxy-3-aryl-1,4-naphthoquinonesHarold E. Zaugg, Richard T. Rapala, and Marlin T. LefflerCite this: J. Am. Chem. Soc. 1948, 70, 10, 3224–3228Publication Date (Print):October 1, 1948Publication History Published online1 May 2002Published inissue 1 October 1948https://pubs.acs.org/doi/10.1021/ja01190a007https://doi.org/10.1021/ja01190a007research-articleACS PublicationsRequest reuse permissionsArticle Views431Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts