gebhart/patrepeval huggingface dataset:
Structure-Specific Endonucleolytic Cleavage of Nucleic Acids by Eubacterial DNA Polymerases (1993)

Previously known 5' exonucleases of several eubacterial DNA polymerases have now been shown to be structure-specific endonucleases that cleave single-stranded DNA or RNA at the bifurcated end of a base-paired duplex. Cleavage was not coupled to synthesis, although primers accelerated the rate of cleavage considerably. The enzyme appeared to gain access to the cleavage site by moving from the free end of a 5' extension to the bifurcation of the duplex, where cleavage took place. Single-stranded 5' arms up to 200 nucleotides long were cleaved from such a duplex. Essentially any linear single-stranded nucleic acid can be targeted for specific cleavage by the 5' nuclease of DNA polymerase through hybridization with an oligonucleotide that converts the desired cleavage site into a substrate.
Time Reversed Acoustics (1997)

The irreversibility of time is a topic generally associated with fundamental physics. Imaging techniques, on the other hand, are usually related to engineering sciences. Remarkably, however, these two domains can be fruitfully connected to yield many applications in medicine, undersea communications, hydrodynamics and material analysis, as well as elegant experiments in pure physics.
Effects of vagal stimulation on induction and termination of atrial fibrillation in an in vivo rabbit heart model. (2010)

Vagus_stim reduces interatrial conduction velocity and significantly shortens atrial ERP, contributing to the induction and duration of AF episodes in the in vivo rabbit heart. This model may be useful for the assessment of autonomic influence on the pathophysiology of AF,
Anti-HIV Activities of Anionic Metalloporphyrins and Related Compounds (1997)

Various water-soluble polysulphonated and polycarboxylated porphyrins and some of their metallated derivatives have been prepared and their antiviral properties against human immunodeficiency virus (HIV-1, HIV-2), simian immunodeficiency virus and other viruses are reported. Besides these polyanionic compounds, two new series of porphyrins were included and studied from the perspective of bio-availability modulation: (i) acefylsulphonamido derivatives endowed with weak acidity properties (deprotonation gives the corresponding anionic derivatives in a pH range 4.5-8.5) and (ii) compounds with the anionic charge transiently masked by esterification (acetoxymethyl- and pivaloyloxymethylesters). Among the more active compounds in inhibiting HIV-induced cytopathic effects, the sulphonated and carboxylated porphyrin complexes were found to interact directly with the HIV protein gp 120 and not with the CD4 cellular receptor.
Insulin-induced egr-1 and c-fos Expression in 32D Cells Requires Insulin Receptor, Shc, and Mitogen-activated Protein Kinase, but Not Insulin Receptor Substrate-1 and Phosphatidylinositol 3-Kinase Activation (1996)

Many studies suggest that insulin utilizes multiple signal transduction pathways. Insulin's effects are initiated by insulin binding to the insulin receptor, resulting in tyrosine phosphorylation of insulin receptor and intracellular substrates, such as insulin receptor substrate-1 (IRS-1), IRS-2, or Shc. We recently demonstrated that immediate-early gene egr-1 transcription was fully induced without phosphorylation of IRS-1 in Chinese hamster ovary cells (Harada, S., Smith, R. M., Smith, J. A., Shah, N. , Hu, D.-Q. & Jarett, L. (1995) J. Biol. Chem. 270, 26632-26638). In the present study, we examined the effects of insulin on immediate-early gene egr-1 and c-fos expression in 32D cells overexpressing the insulin receptor (32D/IR), IRS-1 (32D/IRS), or both (32D/IR+IRS) and compared these effects with insulin-induced tyrosine phosphorylation. Insulin (17 nM) increased egr-1 and c-fos expression in 32D/IR and 32D/IR+IRS cells, but not in parental cells or 32D/IRS cells, as determined by Northern blot analysis. Insulin treatment (5 min at 37 degrees C) markedly increased tyrosine phosphorylation of several proteins, including the insulin receptor, IRS-1, and Shc, in 32D/IR+IRS cells as determined by immunoprecipitation and Western blot analysis with anti-phosphotyrosine antibody. In contrast, only two tyrosine-phosphorylated proteins, i.e. insulin receptor and Shc, were detected in 32D/IR cells. These data suggest that insulin receptor and Shc phosphorylation is necessary for insulin-induced egr-1 and c-fos expression, but IRS-1 phosphorylation is not necessary or sufficient for the expression of these genes. Furthermore, the effect of specific inhibitors on insulin-induced egr-1 expression was examined. Wortmannin (25 nM), a phosphatidylinositol 3-kinase inhibitor, had no effect on insulin-induced egr-1 expression. In contrast, PD 98059 (30 microM), a mitogen-activated protein kinase kinase inhibitor, totally blocked egr-1 expression induced by insulin. These data indicate that mitogen-activated protein kinase activation, but not phosphatidylinositol 3-kinase activation, is involved in insulin-induced egr-1 expression. Taken together, insulin receptor tyrosine phosphorylation, Shc tyrosine phosphorylation, and mitogen-activated protein kinase activation appear to be the signal transduction pathway responsible for insulin-induced egr-1 expression in 32D cells. These data demonstrate that insulin has multiple signal transduction pathways that vary from cell to cell.
Patterns of scAAV Vector Insertion Associated With Oncogenic Events in a Mouse Model for Genotoxicity (2012)

Recombinant adeno-associated virus (rAAV) vectors have gained an extensive record of safety and efficacy in animal models of human disease. Infrequent reports of genotoxicity have been limited to specific vectors associated with excess hepatocellular carcinomas (HCC) in mice. In order to understand potential mechanisms of genotoxicity, and identify patterns of insertion that could promote tumor formation, we compared a self-complementary AAV (scAAV) vector designed to promote insertional activation (scAAV-CBA-null) to a conventional scAAV-CMV-GFP vector. HCC-prone C3H/HeJ mice and severe combined immunodeficiency (SCID) mice were infected with vector plus secondary treatments including partial hepatectomy (HPX) and camptothecin (CPT) to determine the effects of cell cycling and DNA damage on tumor incidence. Infection with either vector led to a significant increase in HCC incidence in male C3H/HeJ mice. Partial HPX after infection reduced HCC incidence in the cytomegalovirus-green fluorescent protein (CMV-GFP)-infected mice, but not in the cognate chicken β-actin (CBA)-null infected group. Tumors from CBA-null infected, hepatectomized mice were more likely to contain significant levels of vector DNA than tumors from the corresponding CMV-GFP-infected group. Most CBA-null vector insertions recovered from tumors were associated with known proto-oncogenes or tumor suppressors. Specific patterns of insertion suggested read-through transcription, enhancer effects, and disruption of tumor suppressors as likely mechanisms for genotoxicity.
Depletion of the Aryl Hydrocarbon Receptor in MDA-MB-231 Human Breast Cancer Cells Altered the Expression of Genes in Key Regulatory Pathways of Cancer (2014)

The aryl hydrocarbon receptor (AhR), a transcription factor that is best known for its role in mediating the toxic responses elicited by poly aromatic hydrocarbons as well as many other environmental factors; is also involved in breast cancer progression. We previously reported that stable knockdown of AhR decreased the tumorigenic properties of the highly metastatic MDA-MB-231 breast cancer cell line; whereas ectopic overexpression of AhR was sufficient to transform immortalized human mammary epithelial cells to exhibit malignant phenotypes. In the present study we investigated the genes that are differentially regulated by AhR and are controlling cellular processes linked to breast cancer. We used Affymetrix Human GeneChip 1.0-ST whole transcriptome arrays to analyze alterations of gene expression resulting from stable AhR knockdown in the MDA-MB-231 breast cancer cell line. The expression of 144 genes was significantly altered with a ≥2.0-fold change and a multiple test corrected p-value ≤0.05, as a result of AhR knockdown. We demonstrate that AhR knockdown alters the expression of several genes known to be linked to cancer. These genes include those involved in tryptophan metabolism (KYNU), cell growth (MUC1 and IL8), cell survival (BIRC3 and BCL3), cell migration and invasion (S100A4 and ABI3), multi-drug resistance (ABCC3) and angiogenesis (VEGFA and CCL2). The identification of the genes and pathways affected by AhR depletion provides new insight into possible molecular events that could explain the reported phenotypic changes. In conclusion AhR knockdown alters the expression of genes known to enhance or inhibit cancer progression; tipping the balance towards a state that counteracts tumor progression.
The Structure of Anthramycin (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Structure of AnthramycinW. Leimgruber, A. D. Batcho, and F. SchenkerCite this: J. Am. Chem. Soc. 1965, 87, 24, 5793–5795Publication Date (Print):December 1, 1965Publication History Published online1 May 2002Published inissue 1 December 1965https://doi.org/10.1021/ja00952a051RIGHTS & PERMISSIONSArticle Views302Altmetric-Citations105LEARN 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 InReddit PDF (346 KB) Get e-Alerts Get e-Alerts
Thrombospondin 1 and Vasoactive Agents Indirectly Alter Tumor Blood Flow (2008)

Nitric oxide (NO) plays important physiological roles in the vasculature to regulate angiogenesis, blood flow, and hemostasis. In solid tumors, NO is generally acknowledged to mediate angiogenic responses to several growth factors. This contrasts with conflicting evidence that NO can acutely increase tumor perfusion through local vasodilation or diminish perfusion by preferential relaxation of peripheral vascular beds outside the tumor. Because thrombospondin 1 (TSP1) is an important physiological antagonist of NO in vascular cells, we examined whether, in addition to inhibiting tumor angiogenesis, TSP1 can acutely regulate tumor blood flow. We assessed this activity of TSP1 in the context of perfusion responses to NO as a vasodilator and epinephrine as a vasoconstrictor. Nitric oxide treatment of wild type and TSP1 null mice decreased perfusion of a syngeneic melanoma, whereas epinephrine transiently increased tumor perfusion. Acute vasoactive responses were also independent of the level of tumor-expressed TSP1 in a melanoma xenograft, but recovery of basal perfusion was modulated by TSP1 expression. In contrast, overexpression of truncated TSP1 lacking part of its CD47 binding domain lacked this modulating activity. These data indicate that TSP1 primarily regulates long-term vascular responses in tumors, in part, because the tumor vasculature has a limited capacity to acutely respond to vasoactive agents.
A Role for Hath1, a bHLH Transcription Factor, in Colon Adenocarcinoma (2005)

A significant reduction or loss of goblet cells is often observed in clinical samples of colon adenocarcinomas, which is the predominant form of colon carcinoma. Mice lacking Math1, a bHLH transcription factor downstream of the Notch signaling pathway, demonstrates that Math1 is necessary for cell fate determination of the intestinal secretory cells, including goblet cells. Examination of Hath1, the human orthologue of Math1, expression in multiple colon tumor samples and colon cancer cell lines reveals a dramatic decrease in Hath1 expression in colon tumor samples and colon cancer cell lines. Hath1 expression in the HT29 colon cancer cell line can significantly inhibit its proliferation and anchorage-independent growth both in vitro and in vivo. At the molecular level, Hath1 may regulate the expression of MUC2, a mucin secreted by goblet cells, and Hath1 may also be a novel factor normally repressed as a consequence of activation of the Wnt signaling pathway, which has been clearly implicated in colon tumorigenesis.
Molecular‐Size Reduction of a Potent CXCR4‐Chemokine Antagonist Using Orthogonal Combination of Conformation‐ and Sequence‐Based Libraries (2003)

Efficient downsizing of peptides: By combination of two orthogonal “conformation-based” and “sequence-based” libraries, the cyclic pentapeptide cyclo(-L-Nal 1-Gly 2-D-Tyr 3-L-Arg 4-L-Arg 5-) (Nal=L-3-(2-naphthyl)alanine; see overlay of the five lowest energy structures), which exhibited strong CXCR4 antagonism (IC50=4 nM) comparable to that of a 14-residue lead compound, T140, was discovered. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2003/z51024_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Requirements for nuclear localization of the Lsm2-8p complex and competition between nuclear and cytoplasmic Lsm complexes (2007)

Sm-like (Lsm) proteins are ubiquitous, multifunctional proteins that are involved in the processing and/or turnover of many RNAs. In eukaryotes, a hetero-heptameric complex of seven Lsm proteins (Lsm2-8) affects the processing of small stable RNAs and pre-mRNAs in the nucleus, whereas a different hetero-heptameric complex of Lsm proteins (Lsm1-7) promotes mRNA decapping and decay in the cytoplasm. These two complexes have six constituent proteins in common, yet localize to separate cellular compartments and perform apparently disparate functions. Little is known about the biogenesis of the Lsm complexes, or how they are recruited to different cellular compartments. We show that, in yeast, the nuclear accumulation of Lsm proteins depends on complex formation and that the Lsm8p subunit plays a crucial role. The nuclear localization of Lsm8p is itself most strongly influenced by Lsm2p and Lsm4p, its presumed neighbours in the Lsm2-8p complex. Furthermore, overexpression and depletion experiments imply that Lsm1p and Lsm8p act competitively with respect to the localization of the two complexes, suggesting a potential mechanism for co-regulation of nuclear and cytoplasmic RNA processing. A shift of Lsm proteins from the nucleus to the cytoplasm under stress conditions indicates that this competition is biologically significant.
DOEGO85004_1: Final Non-proprietary Technical Report, Generating Process and Economic Data for Preliminary Design of PureVision Biorefineries DOEGO85004_2: One Original Final Proprietary Technical Report to be mailed to DOE Golden. (2008)

The overall objective of the project was to define a two-stage reactive fractionation process for converting corn stover into a solid cellulose stream and two liquid streams containing mostly hemicellulosic sugars and lignin, respectively. Toward this goal, biomass fractionation was conducted using a small continuous pilot unit with a nominal capacity of 100 pounds per day of dry biomass to generate performance data using primarily corn stover as feedstock. In the course of the program, the PureVision process was optimized for efficient hemicellulose hydrolysis in the first stage employing autohydrolysis and delignification in the second stage using sodium hydroxide as a catalyst. The remaining cellulose was deemed to be an excellent substrate for producing fermentation sugars, requiring 40% less enzymes for hydrolysis than conventional pretreatment systems using dilute acid. The fractionated cellulose was also determined to have potential higher-value applications as a pulp product. The lignin coproduct was determined to be substantially lower in molecular weight (MW) compared to lignins produced in the kraft or sulfite pulping processes. This low-MW lignin can be used as a feed and concrete binder and as an intermediate for producing a range of high-value products including phenolic resins. This research adds to the understanding of the biomass conversion area in that a new process was developed in the true spirit of biorefineries. The work completed successfully demonstrated the technical effectiveness of the process at the pilot level indicating the technology is ready to advance to a 2–3 ton per day scale. No technical showstoppers are anticipated in scaling up the PureVision fractionation process to commercial scale. Also, economic feasibility of using the PureVision process in a commercial-scale biorefinery was investigated and the minimum ethanol selling price for the PureVision process was calculated to be $0.94/gal ethanol vs. $1.07/gal ethanol for the NREL process. Thus, the PureVision process is economically attractive. Given its technical and economic feasibility, the project is of benefit to the public in the following ways: 1) it demonstrated a novel biomass fractionation process that can provide domestic supply of renewable transportation fuel from all three biomass components (cellulose, hemicellulose and lignin), 2) the lignin stream from the process has many higher-value applications beyond simply burning the lignin for energy as proposed by competing technologies, 3) it can be deployed in rural areas and create jobs in these areas, and 3) it can add to the nation’s economy and security.
Dose‐ and volume dependent‐response to intramuscular injection of botulinum neurotoxin‐A optimizes muscle force decrement in mice (2011)

Botulinum neurotoxin-A (BoNTA) is a potent neurotoxin used to alter muscle tone to manage spasticity and to provide tendon bioprotection; however, the appropriate dose and injection volume to administer is not defined. Male mice (n = 120) received BoNTA injections into one gastrocnemius with either a constant volume (10 µl) with a variable dose (1, 3, 6 U/kg) or a constant dose (3 U/kg) in a variable volume (2.5, 5, 10, 20, 30 µl). Electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass were measured in the ipsilateral and contralateral limbs at 1, 2, 4, or 12 weeks post-injection. MFG and EMG responses decreased to approximately 40% of contralateral after a 1 U/kg injection and 0% of contralateral by 3 and 6 U/kg injection at 1 week after injection. Neuromuscular blockade was greatest with a 10 µl injection volume. MFG, EMG examination, and wet muscle mass reached contralateral values 12 weeks after injection for all injection doses and volumes tested. Effective injection doses and volumes were identified for producing full and partial neuromuscular blockade in the mouse gastrocnemius. These findings have important clinical implications in the intramuscular administration of BoNTA to manage muscle tone.
Treatment outcomes and clinicopathologic characteristics of triple‐negative breast cancer patients who received platinum‐containing chemotherapy (2008)

The aim of this study was to evaluate the role of platinum-containing chemotherapy for metastatic triple-negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression-free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane-platinum chemotherapy as the first- or second-line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum-containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor-2 (HER2) receptor status received taxane-platinum regimen as the first- or second-line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p = 0.037) and overall survival (OS) (21 vs. 56 months, p = 0.030) differed significantly between patients with TNBC and non-TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum-containing chemotherapy, patients with TNBC had a shorter OS than patients with non-TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted.
Improvement of Alveolar Glutathione and Lung Function but Not Oxidative State in Cystic Fibrosis (2004)

Chronic neutrophilic inflammation leads to oxidative damage, which may play an important role in the pathogenesis of cystic fibrosis lung disease. Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in patients with cystic fibrosis. Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels, lung function, and oxidative status. Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari LC Star nebulizer (Allergy Asthma Technology, Morton Grove, IL) connected to an AKITA inhalation device (Inamed, Gauting, Germany) was determined in six patients. In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg of glutathione. Intrathoracic deposition was 86.3 +/- 1.4% of the emitted dose. Glutathione concentration in lavage 1 hour postinhalation was increased three- to fourfold and was still almost doubled 12 hours postinhalation. FEV(1) transiently dropped after inhalation but increased compared with pretreatment values after 14 days (p < 0.001). This improvement was not related to the lavage content of oxidized proteins and lipids, which did not change with treatment. These results show that, using a new inhalation device with high efficacy, glutathione treatment of the lower airways is feasible. Reversion of markers of oxidative injury may need longer treatment, higher doses, or different types of antioxidants.