gebhart/patrepeval huggingface dataset:
Controlled Aspiration of Subretinal Fluid in the Diagnosis of Carcinoma Metastatic to the Choroid (1984)

Carcinoma metastatic to the choroid was diagnosed in three patients by cytopathologic examination of subretinal fluid. The specimen was obtained using a scleral depressor modified to allow controlled aspiration of subretinal fluid through a sharp, angled, 30-gauge needle. This new method provides a useful tool for accurate diagnosis of carcinoma metastatic to the choroid in cases where the diagnosis is in question.
Transcriptional regulation of vascular endothelial growth factor by estradiol and tamoxifen in breast cancer cells: a complex interplay between estrogen receptors alpha and beta. (2002)

Vascular endothelial growth factor (VEGF) is a potent angiogenic and prognostic factor for many tumors, including those of endocrine-responsive tissues such as the breast and uterus. Recent studies indicate that 17beta-estradiol (E(2)) modulates VEGF expression in breast and uterine cells, involving transcriptional activation through estrogen receptor (ER) alpha. However, molecular mechanisms of VEGF regulation mediated by the two ER subtypes and the potential role of ERbeta in the control of breast cancer angiogenesis have not yet been investigated. In transient transfection assays using the VEGF(-2275/+54) promoter-luciferase construct, E(2) (1 nM) increased transcription activity in MCF-7 cells (either untransfected or cotransfected with ERalpha) and it increased transcription activity in MDA-MB-231 cells cotransfected with ERalpha or ERbeta (1.8- and 2-fold induction, respectively). The positive effect was abolished when MCF-7 cells were treated with pure antiestrogen ICI 182,780 or the agonist/antagonist tamoxifen (1 micro M). To identify response elements involved in this transcriptional regulation, MCF-7 or MDA-MB-231 cells were transfected with several deletion constructs of the VEGF promoter. Deletion of 1.2-2.3 kb upstream to the transcription start in the VEGF promoter abrogated E(2)-dependent transcription in these cells. This region contains an imperfect estrogen-responsive element (ERE), ERE1520, and one activator protein 1 site. Transfection of MCF-7 cells (ERalpha) with the ERE1520-luciferase construct conferred transcriptional activity with 1 nM E(2) (1.9-fold induction). Also, the imperfect ERE formed a complex with ERalpha or ERbeta proteins in gel shift assay using MCF-7 or MDA-MB-231 nuclear extracts. In contrast to ERalpha, ERbeta could transactivate VEGF reporter construct in MDA-MB-231 cells, in the presence of E(2) or tamoxifen, suggesting different transactivational mechanisms between ERalpha and ERbeta in the presence of tamoxifen. Interestingly, E(2) inhibited VEGF transcription in MCF-7 cells transfected with ERbeta or MDA-MB-231 cells cotransfected with ERalpha and ERbeta, suggesting that heterodimerization of ERalpha/ERbeta has the ability to inhibit E(2)-induced VEGF expression in breast cancer cells. These results demonstrate that VEGF is a target gene for ERalpha and ERbeta in breast cancer cells; it remains to be determined whether ERalpha and ERbeta expression in breast biopsies correlates with VEGF expression and vascular density.
Identifying Semantically Deviating Outlier Documents (2017)

A document outlier is a document that substantially deviates in semantics from the majority ones in a corpus. Automatic identification of document outliers can be valuable in many applications, such as screening health records for medical mistakes. In this paper, we study the problem of mining semantically deviating document outliers in a given corpus. We develop a generative model to identify frequent and characteristic semantic regions in the word embedding space to represent the given corpus, and a robust outlierness measure which is resistant to noisy content in documents. Experiments conducted on two real-world textual data sets show that our method can achieve an up to 135% improvement over baselines in terms of recall at top-1% of the outlier ranking.
Locating Congested Segments over the Internet Based on Multiple End-to-End Path Measurements (2006)

Since congestion is very likely to happen in the Internet, locating congested areas (path segments) along a congested path is vital to appropriate actions by Internet Service Providers to mitigate or prevent network performance degradation.We propose a practical method to locate congested segments by actively measuring one-way end-to-end packet losses on appropriate paths from multiple origins to multiple destinations, using a network tomographic approach.Then we conduct a long-term experiment measuring packet losses on multiple paths over the Japanese commercial Internet.The experimental results indicate that the proposed method is able to precisely locate congested segments.Some findings on congestion over the Japan Internet are also given based on the experiment.
Molecular Cloning of a Glucoamylase producing Gene in the Yeast<i>Saccharomyces</i> (1983)

Journal Article Molecular Cloning of a Glucoamylase producing Gene in the Yeast Saccharomyces Get access Ichiro Yamashita, Ichiro Yamashita Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Shitami, Saijo-cho, Higashi- Hiroshima 724, Japan Search for other works by this author on: Oxford Academic Google Scholar Sakuzo Fukui Sakuzo Fukui Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Shitami, Saijo-cho, Higashi- Hiroshima 724, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 47, Issue 11, 1 November 1983, Pages 2689–2692, https://doi.org/10.1080/00021369.1983.10866019 Published: 01 November 1983 Article history Received: 13 June 1983 Published: 01 November 1983
Chemical and Enzymatic Synthesis of Fluorinated‐Dehydroalanine‐Containing Peptides (2003)

Michael acceptors have long been recognized as reactive functionalities that may link a biologically active molecule to its cellular target. 1,2-Dehydro amino acids are potential Michael acceptors present in a large number of natural products, but their reactivity is modulated by the deactivating nature of the alpha-amino group engaged in an amide bond. We describe here the preparation of 3-fluoro-1,2-dehydroalanine moieties within peptides that significantly enhance the reactivity of the Michael acceptor. Two different routes were designed to access these compounds, one relying on chemical means to introduce the desired functionality and the second taking advantage of a peptide epimerase. In the chemical approach, the fluoro-Pummerer reaction of cysteine derivatives afforded 3-fluorocysteine residues that were oxidized to the corresponding sulfoxides, followed by thermolytic elimination to provide the desired 3-fluorodehydroalanines. The mechanism of the fluoro-Pummerer reaction was investigated and several possible pathways were ruled out. The enzymatic approach utilized the dipeptide epimerase YcjG from Escherichia coli. Difluorinated alanine was incorporated at the C terminus of a dipeptide by chemical means. The resulting peptide proved to be a substrate for YcjG, which catalyzed fluoride elimination to provide the 3-fluorodehydroalanine-containing peptide. Mechanistic investigations showed that fluoride elimination occurred faster than epimerization and at a rate close to that of epimerization of Ala-Ala.
Asymmetric Aldol Reactions Using (<i>S</i>,<i>S</i>)-(<i>+</i>)-Pseudoephedrine-Based Amides:  Stereoselective Synthesis of α-Methyl-β-hydroxy Acids, Esters, Ketones, and 1,3-Syn and 1,3-Anti Diols (2000)

A very efficient method for performing stereoselective aldol reactions is reported. The reaction of (S, S)-(+)-pseudoephedrine-derived propionamide enolates with several aldehydes yielded exclusively one of the four possible diastereomers in good yields, although transmetalation of the firstly generated lithium enolate with a zirconium(II) salt, prior to the addition of the aldehyde, is necessary in order to achieve high syn selectivity. The so-formed syn-alpha-methyl-beta-hydroxy amides were transformed into other valuable chiral nonracemic synthons such as alpha-methyl-beta-hydroxyacids, esters, and ketones. Finally, a stereocontrolled reduction procedure starting from the so-obtained alpha-methyl-beta-hydroxy ketones has been developed allowing the synthesis of either 1,3-syn- or 1,3-anti-alpha-methyl-1,3-diols in almost enantiopure form by choosing the appropriate reaction conditions.
Cloning and expression of a type 1 fimbrial subunit of Actinomyces viscosus T14V (1987)

The type 1 fimbriae of Actinomyces viscosus mediate the adherence of this organism to saliva-treated hydroxyapatite. The gene encoding a putative subunit of this fimbrial adhesin was cloned in Escherichia coli, and its product was examined. A. viscosus T14V chromosomal DNA was partially restricted with Sau3AI and cloned into E. coli JM109 by using the plasmid vector pUC13. Two clones, each containing a different DNA insert with a common 4.1-kilobase region, reacted in colony immunoassays with specific polyclonal as well as monoclonal antibodies directed against A. viscosus T14V type 1 fimbriae. Western blot analysis revealed the expression of a 65-kilodalton protein that migrated slightly behind an antigenically similar protein from native type 1 fimbriae. Deletion analysis showed that the gene encoding the cloned protein was localized on a 1.9-kilobase PstI-BamHI fragment and that transcription was dependent on the lac promoter of the vector. The cloned fimbrial protein was purified from the E. coli cytoplasmic fraction by ion-exchange, immunoaffinity, and gel permeation chromatography. Rabbit antibodies prepared against the cloned protein and against purified A. viscosus type 1 fimbriae gave similar patterns with partially dissociated type 1 fimbriae after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The data therefore provide evidence that the gene cloned encodes a subunit of this fimbrial adhesin.
Capping of tobacco mosaic virus RNA. Analysis of viral-coded guanylyltransferase-like activity. (1990)

The 5' end of tobacco mosaic virus (TMV) genomic RNA is capped with 7-methylguanosine. A virus-coded polypeptide with guanylyltransferase activity has been investigated. This enzyme is responsible for forming the 5'----5' linkage of guanosine 5'-monophosphate to the 5'-diphosphate of an acceptor RNA, thereby forming the cap. A critical step in the mechanism for cap formation in the eukaryotic nucleus is for guanylyltransferase to bind covalently to guanosine 5'-monophosphate with the hydrolysis of pyrophosphate when guanosine 5'-triphosphate is the substrate. The TMV 126-kilodalton protein, which is most probably a component of the TMV replicase, was found to have this activity. The mechanism of this reaction has been characterized biochemically.
Enhanced Stem Cell Differentiation and Immunopurification of Genome Engineered Human Retinal Ganglion Cells (2017)

Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols are often lacking. Here, we describe the generation of clustered regularly-interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in embryonic stem cell lines in which tdTomato and a unique cell-surface protein, THY1.2, are expressed under the control of the retinal ganglion cell (RGC)-enriched gene BRN3B. Using these reporter cell lines, we greatly improved adherent stem cell differentiation to the RGC lineage by optimizing a novel combination of small molecules and established an anti-THY1.2-based protocol that allows for large-scale RGC immunopurification. RNA-sequencing confirmed the similarity of the stem cell-derived RGCs to their endogenous human counterparts. Additionally, we developed an in vitro axonal injury model suitable for studying signaling pathways and mechanisms of human RGC cell death and for high-throughput screening for neuroprotective compounds. Using this system in combination with RNAi-based knockdown, we show that knockdown of dual leucine kinase (DLK) promotes survival of human RGCs, expanding to the human system prior reports that DLK inhibition is neuroprotective for murine RGCs. These improvements will facilitate the development and use of large-scale experimental paradigms that require numbers of pure RGCs that were not previously obtainable. Stem Cells Translational Medicine 2017;6:1972-1986.
Biosurfactants: A New Pharmaceutical Additive for Solubility Enhancement and Pharmaceutical Development (2013)

Biosurfactants are structurally diverse group of surface-active substances produced by microorganisms. At present, biosurfactants have gained importance in the pharmaceutical, biomedical, cosmetic and food industry, with a high added value, are still developing. Surfactants have numerous uses in pharmaceuticals, for solubilization of hydrophobic drugs in aqueous media, as components of emulsion or surfactant self-assembly vehicles for oral and transdermal drug delivery, as plasticizers in semisolid delivery systems, and agents to improve drug absorption and as penetration enhancer. Many pharmaceuticalgrade surfactants consist of saccharide- or polyol-fatty acid esters or fatty alcohol ethers that are biosurfactant. This article describes classical and new biosurfactants’ producing bacteria along with their significant role as pharmaceutical additives in development of pharmaceuticals and to encourage its use in solubility or bioavailability enhancement of poorly soluble drugs.
Mutation of the Lipopolysaccharide Core Glycosyltransferase Encoded by <i>waaG</i> Destabilizes the Outer Membrane of <i>Escherichia coli</i> by Interfering with Core Phosphorylation (2000)

In Escherichia coli, phosphoryl substituents in the lipopolysaccharide core region are essential for outer membrane stability. Mutation of the core glucosyltransferase encoded by waaG (formerly rfaG) resulted in lipopolysaccharide truncated immediately after the inner core heptose residues, which serve as the sites for phosphorylation. Surprisingly, mutation of waaG also destabilized the outer membrane. Structural analyses of waaG mutant lipopolysaccharide showed that the cause for this phenotype was a decrease in core phosphorylation, an unexpected side effect of the waaG mutation.
Design and Validation of a New Immunoassay for Soluble Forms of Thrombomodulin and Studies on Plasma (1994)

Thrombomodulin (TM), purified from human placental homogeneate by affinity chromatography on DIP-Thrombin agarose, was used to develop monoclonal antibodies (MAbs). Two of them, 3E2 and 24FM (both IgG1, K), which were not calcium-dependent, were found convenient for developing a two-site enzyme immunoassay. Testing of recombinant and truncated forms of TM26 demonstrated that the species containing the amino terminus including the lectin-like domain and the epidermal growth factor (EGF)-like domains 1-4 were fully measured. The working range was from 2 to 100 ng/ml with a detection threshold of 2 ng/ml. Intraassay and interassay reproducibilities were, respectively, below 7.4% and 8.6%, whereas recovery of purified TM was between 88 and 114% in plasma. Mean plasma concentration was 42.1 (+/- 11.3) ng/ml (males 51.8 +/- 7.9 ng/ml, females 34.8 +/- 7.8 ng/ml) and it was established on 62 normal individuals between the ages of 21 and 55 (28 males and 34 females). This new assay is a convenient tool for measuring plasma TM and establishing its diagnostic and predictive value in diseases associated to endothelial damage.
A Conserved Histidine in Insulin Is Required for the Foldability of Human Proinsulin (2006)

The insulins of eutherian mammals contain histidines at positions B5 and B10. The role of His(B10) is well defined: although not required in the mature hormone for receptor binding, in the islet beta cell this side chain functions in targeting proinsulin to glucose-regulated secretory granules and provides axial zincbinding sites in storage hexamers. In contrast, the role of His(B5) is less well understood. Here, we demonstrate that its substitution with Ala markedly impairs insulin chain combination in vitro and blocks the folding and secretion of human proinsulin in a transfected mammalian cell line. The structure and stability of an Ala(B5)-insulin analog were investigated in an engineered monomer (DKP-insulin). Despite its impaired foldability, the structure of the Ala(B5) analog retains a native-like T-state conformation. At the site of substitution, interchain nuclear Overhauser effects are observed between the methyl resonance of Ala(B5) and side chains in the A chain; these nuclear Overhauser effects resemble those characteristic of His(B5) in native insulin. Substantial receptor binding activity is retained (80 +/- 10% relative to the parent monomer). Although the thermodynamic stability of the Ala(B5) analog is decreased (DeltaDeltaG(u) = 1.7 +/- 0.1 kcal/mol), consistent with loss of His(B5)-related interchain packing and hydrogen bonds, control studies suggest that this decrement cannot account for its impaired foldability. We propose that nascent long-range interactions by His(B5) facilitate alignment of Cys(A7) and Cys(B7) in protein-folding intermediates; its conservation thus reflects mechanisms of oxidative folding rather than structure-function relationships in the native state.
A High Proportion of Hybridomas Raised to a Plant Extract Secrete Antibody to Arabinose or Galactose (1984)

A high proportion of hybridomas, obtained from mice immunized with style extracts prepared from mature flowers of an ornamental tobacco, Nicotiana alata, secrete antibody to arabinogalactan protein (AGP). The specificity of the antibodies secreted by three cloned cell lines is primarily directed to beta-d-galactopyranose and alpha-l-arabinofuranose; antibodies from two cell lines preferentially bind beta-d-galactopyranose residues and antibodies from the other cell line preferentially bind alpha-l-arabinofuranose. As AGPs are components of most plant tissues and exudates, it is likely that attempts to raise monoclonal antibodies to other plant extracts will result in hybridomas producing antibodies to AGPs.
Online Detection of Loss of Synchronism Using Energy Function Criterion (2005)

Maintaining dynamic security of a power system subjected to large disturbances is of utmost importance. Fast and accurate online detection of instability is essential in initiating certain emergency control measures. The techniques reported in the literature involve mainly the application of global phasor measurements and heuristic algorithms. In this paper, an accurate technique for the online detection of loss of synchronism based on voltage and current measurements in a line is presented. The technique makes use of the concept of potential energy in a line. The conditions for the system instability are derived from energy function analysis. However, no assumptions are made regarding the power-angle relationship in a line, nor are any data on the system equivalents necessary in implementing the detection scheme.
An indirect impedance characterization method for monolithic THz antennas (2011)

We present an impedance characterization method for THz antennas using coplanar probe measurements. The antenna structure, which is typically monolithically integrated with detector diodes, is represented as a two-port network. The impedance seen by the diode can be analytically extracted using reflection coefficient measurements from the other remote location of the antenna. The diode port is replaced with three terminations (short, open, and a resistive load) and measured S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> data is used to compute the impedance seen by the diode. The results show that the approach gives an accurate estimate of the antenna impedance except when the electrical length between two ports is near a multiple of one-half wavelength.
The cytoplasmic tail of the mannose 6-phosphate/insulin-like growth factor-II receptor has two signals for lysosomal enzyme sorting in the Golgi. (1992)

The mannose 6-phosphate/insulin-like growth factor-II (Man-6-P/IGF-II) receptor is known to cycle between the Golgi, endosomes, and the plasma membrane. In the Golgi the receptor binds newly synthesized lysosomal enzymes and transports them directly to an endosomal (prelysosomal) compartment without traversing the plasma membrane. Deletion of the carboxyl-terminal Leu-Leu-His-Val residues of the 163 amino acid cytoplasmic tail of the bovine Man-6-P/IGF-II receptor partially impaired this function, resulting in the diversion of a portion of the receptor-ligand complexes to the cell surface, where they were endocytosed. The same phenotype was observed when 134 residues of the cytoplasmic tail were deleted from the carboxyl terminus. Disruption of the Tyr24-Lys-Tyr-Ser-Lys-Val29 plasma membrane internalization signal alone had little effect on Golgi sorting, but when combined with either deletion resulted in a complete loss of this function. The mutant receptors retained the ability to recycle to the Golgi and bind cathepsin D. These results indicate that the cytoplasmic tail of the Man-6-P/IGF-II receptor contains two signals that contribute to Golgi sorting, presumably by interacting with the Golgi clathrin-coated pit adaptor proteins. The Leu-Leu-containing sequence represents a novel motif for mediating interaction with Golgi adaptor proteins.
Steady-State and Stopped-Flow Kinetic Studies of Three <i>Escherichia coli</i> NfsB Mutants with Enhanced Activity for the Prodrug CB1954 (2009)

The enzyme nitroreductase, NfsB, from Escherichia coli has entered clinical trials for cancer gene therapy with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. However, CB1954 is a poor substrate for the enzyme. Previously we made several NfsB mutants that show better activity with CB1954 in a cell-killing assay in E. coli. Here we compare the kinetic parameters of wild-type NfsB with CB1954 to those of the most active single, double, and triple mutants isolated to date. For wild-type NfsB the global kinetic parameters for both k(cat) and K(m) for CB1954 are about 20-fold higher than previously estimated; however, the measured specificity constant, k(cat)/K(m) is the same. All of the mutants are more active with CB1954 than the wild-type enzyme, the most active mutant showing about 100-fold improved specificity constant with CB1954 over the wild-type protein with little effect on k(cat). This enhancement in specificity constants for the mutants is not seen with the antibiotic nitrofurazone as substrate, leading to reversed nitroaromatic substrate selectivity for the double and triple mutants. However, similar enhancements in specificity constants are found with the quinone menadione. Stopped-flow kinetic studies suggest that the rate-determining step of the reaction is likely to be the release of products. The most active mutant is also selective for the 4-nitro group of CB1954, rather than the 2-nitro group, giving the more cytotoxic reduction product. The double and triple mutants should be much more effective enzymes for use with CB1954 in prodrug-activation gene therapy.