gebhart/patrepeval huggingface dataset:
Metabolic Labeling of Caenorhabditis elegans Primary Embryonic Cells with Azido-Sugars as a Tool for Glycoprotein Discovery (2012)

Glycobiology research with Caenorhabditis elegans (C. elegans) has benefitted from the numerous genetic and cell biology tools available in this system. However, the lack of a cell line and the relative inaccessibility of C. elegans somatic cells in vivo have limited the biochemical approaches available in this model. Here we report that C. elegans primary embryonic cells in culture incorporate azido-sugar analogs of N-acetylgalactosamine (GalNAc) and N-acetylglucosamine (GlcNAc), and that the labeled glycoproteins can be analyzed by mass spectrometry. By using this metabolic labeling approach, we have identified a set of novel C. elegans glycoprotein candidates, which include several mitochondrially-annotated proteins. This observation was unexpected given that mitochondrial glycoproteins have only rarely been reported, and it suggests that glycosylation of mitochondrially-annotated proteins might occur more frequently than previously thought. Using independent experimental strategies, we validated a subset of our glycoprotein candidates. These include a mitochondrial, atypical glycoprotein (ATP synthase α-subunit), a predicted glycoprotein (aspartyl protease, ASP-4), and a protein family with established glycosylation in other species (actin). Additionally, we observed a glycosylated isoform of ATP synthase α-subunit in bovine heart tissue and a primate cell line (COS-7). Overall, our finding that C. elegans primary embryonic cells are amenable to metabolic labeling demonstrates that biochemical studies in C. elegans are feasible, which opens the door to labeling C. elegans cells with other radioactive or azido-substrates and should enable the identification of additional post-translationally modified targets and analysis of the genes required for their modification using C. elegans mutant libraries.
Generation of transposon insertion mutant libraries for Gram-positive bacteria by electroporation of phage Mu DNA transposition complexes (2005)

Transposon mutagenesis is a powerful technique for generating collections of insertion mutants for genetic studies. This paper describes how phage Mu DNA transposition complexes, transpososomes, can be exploited for gene delivery to efficiently introduce selectable markers to genomes of Gram-positive bacteria. Mu transpososomes were assembled in vitro with custom-designed mini-Mu transposons, concentrated, and electroporated into cells of three Gram-positive bacterial species: Staphylococcus aureus, Streptococcus pyogenes and Streptococcus suis. Within cells, the complexes reproduced an authentic DNA transposition reaction and integrated the delivered transposons into the bacterial genomes, yielding single-copy insertions. The integration efficiency among different species and strains of Gram-positive bacteria ranged from 1x10(1) to 2x10(4) c.f.u. (mug introduced transposon DNA)(-1). The strategy should be applicable to a variety of other Gram-positive species after initial optimization of certain key factors affecting transposon delivery, such as the preparation method of competent cells and physical parameters of electroporation. This study extends the scope of the Mu transpososome delivery-based genomic DNA integration strategy to Gram-positive bacteria. Thus, a straightforward generation of sizeable mutant banks is feasible for these bacteria, potentiating several types of genomic-level approaches for studies of a variety of important bacterial processes, such as pathogenicity.
Origins and Evolution of Antibiotic Resistance (2010)

Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.
Equine Herpesvirus Protein E10 Induces Membrane Recruitment and Phosphorylation of Its Cellular Homologue, Bcl-10 (2001)

v-E10, a caspase recruitment domain (CARD)-containing gene product of equine herpesvirus 2, is the viral homologue of the bcl-10 protein whose gene was found to be translocated in mucosa-associated lymphoid tissue (MALT) lymphomas. v-E10 efficiently activates the c-jun NH(2)-terminal kinase (JNK), p38 stress kinase, and the nuclear factor (NF)-kappaB transcriptional pathway and interacts with its cellular homologue, bcl-10, via a CARD-mediated interaction. Here we demonstrate that v-E10 contains a COOH-terminal geranylgeranylation consensus site which is responsible for its plasma membrane localization. Expression of v-E10 induces hyperphosphorylation and redistribution of bcl-10 from the cytoplasm to the plasma membrane, a process which is dependent on the intactness of the v-E10 CARD motif. Both membrane localization and a functional CARD motif are important for v-E10-mediated NF-kappaB induction, but not for JNK activation, which instead requires a functional v-E10 binding site for tumor necrosis factor receptor-associated factor (TRAF)6. Moreover, v-E10-induced NF-kappaB activation is inhibited by a dominant negative version of the bcl-10 binding protein TRAF1, suggesting that v-E10-induced membrane recruitment of cellular bcl-10 induces constitutive TRAF-mediated NF-kappaB activation.
The Role of Genetic Variation in Thiopurine Methyltransferase Activity and the Efficacy and/or Side Effects of Azathioprine Therapy in Dermatologic Patients (1995)

The TPMTH heterozygotes may be at increased risk for myelosuppression with standard, empiric doses of azathioprine. On the other hand, homozygotes for TPMTH, particularly those with TPMT levels at the upper end of the homozygous range, may have a poor clinical response to azathioprine due to inadequate empiric dosing.
Clustering versus faceted categories for information exploration (2006)

article Clustering versus faceted categories for information exploration Author: Marti A. Hearst University of California, Berkeley University of California, BerkeleyView Profile Authors Info & Claims Communications of the ACMVolume 49Issue 4April 2006 pp 59–61https://doi.org/10.1145/1121949.1121983Published:01 April 2006Publication History 262citation4,167DownloadsMetricsTotal Citations262Total Downloads4,167Last 12 Months95Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Reactivity of Vinyl-Terminated Self-Assembled Monolayers on Gold:  Olefin Cross-Metathesis Reactions (2003)

Introduction of various organic functional groups onto organic thin films is a first step in their applications to sensors, catalysis, and nanotechnology in general. In this paper, we studied the reactivity of vinyl-terminated self-assembled monolayers (SAMs) of undec-10-ene-1-thiol on gold toward olefin cross-metathesis (CM). Vinyl groups on SAMs were successfully converted into α,β-unsaturated carbonyl groups by CM with acrylic acid, methyl acrylate, and acrylamide, and CM was confirmed by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and contact-angle measurement. Ruthenium-catalyzed olefin CM has offered a versatile strategy for functionalization in solution chemistry with mild reaction conditions and a high compatibility in functional groups. Our result shows that various useful functional groups can be introduced to SAMs on gold (and other solid surfaces) by olefin CM and suggests an alternative to the synthesis of desired molecules in solution.
Stochastic Rank-1 Bandits (2017)

We propose stochastic rank-$1$ bandits, a class of online learning problems where at each step a learning agent chooses a pair of row and column arms, and receives the product of their values as a reward. The main challenge of the problem is that the individual values of the row and column are unobserved. We assume that these values are stochastic and drawn independently. We propose a computationally-efficient algorithm for solving our problem, which we call Rank1Elim. We derive a $O((K + L) (1 / \Delta) \log n)$ upper bound on its $n$-step regret, where $K$ is the number of rows, $L$ is the number of columns, and $\Delta$ is the minimum of the row and column gaps; under the assumption that the mean row and column rewards are bounded away from zero. To the best of our knowledge, we present the first bandit algorithm that finds the maximum entry of a rank-$1$ matrix whose regret is linear in $K + L$, $1 / \Delta$, and $\log n$. We also derive a nearly matching lower bound. Finally, we evaluate Rank1Elim empirically on multiple problems. We observe that it leverages the structure of our problems and can learn near-optimal solutions even if our modeling assumptions are mildly violated.
Intercellular Bridges in Vertebrate Gastrulation (2011)

The developing zebrafish embryo has been the subject of many studies of regional patterning, stereotypical cell movements and changes in cell shape. To better study the morphological features of cells during gastrulation, we generated mosaic embryos expressing membrane attached Dendra2 to highlight cellular boundaries. We find that intercellular bridges join a significant fraction of epiblast cells in the zebrafish embryo, reaching several cell diameters in length and spanning across different regions of the developing embryos. These intercellular bridges are distinct from the cellular protrusions previously reported as extending from hypoblast cells (1-2 cellular diameters in length) or epiblast cells (which were shorter). Most of the intercellular bridges were formed at pre-gastrula stages by the daughters of a dividing cell maintaining a membrane tether as they move apart after mitosis. These intercellular bridges persist during gastrulation and can mediate the transfer of proteins between distant cells. These findings reveal a surprising feature of the cellular landscape in zebrafish embryos and open new possibilities for cell-cell communication during gastrulation, with implications for modeling, cellular mechanics, and morphogenetic signaling.
New Chiral Diphosphine Ligands Designed to have a Narrow Dihedral Angle in the Biaryl Backbone (2001)

A series of novel optically active diphosphine ligands, (4,4′-bi-1,3-benzodioxole)-5,5′-diylbis(diarylphosphine)s (6), which are called SEGPHOS, has been designed and synthesized with dihedral angles in the Ru complexes being less than that in the corresponding BINAP-Ru complex. The stereorecognition abilities of SEGPHOS-Ru complex catalysts in the asymmetric catalytic hydrogenation of a wide variety of carbonyl compounds are superior to those observed with BINAP-Ru complex catalysts.
[Surgical management of naso-orbital-ethmoid fractures]. (2005)

The satisfactory correction of NOE fracture and subsequent enophthalmos/dystopia and telecanthus can be achieved with elective surgery in most cases.
Molecular cloning and expression of the genes encoding theEscherichia coliK4 capsular polysaccharide, a fructose-substituted chondroitin (1990)

The majority of capsular polysaccharides (K antigens) are linear molecules and their genes have a common functional organisation encoding common steps in capsule biogenesis. However, the K4 antigen is a substituted polymer composed of a chondroitin backbone with a fructose side chain. In order to determine whether K4 biosynthesis uses these common mechanisms the K4 antigen genes were cloned. DNA probes taken from the two conserved regions of the Kl genes were used to isolate one plasmid, pRDl, homologous to both probes. Immunological analysis was used to show that pRDl directs the production of the substituted K4 antigen on the cell surface. Southern hybridisation was used to show that the cloned genes are organised in the same way as other K antigen gene clusters. We conclude that the branched K4 antigen is handled by the same post-polymerization mechanisms as other linear K antigens.
Nonclinical Pharmacology/Toxicology Study of AAV8.TBG.mLDLR and AAV8.TBG.hLDLR in a Mouse Model of Homozygous Familial Hypercholesterolemia (2017)

The homozygous form of familial hypercholesterolemia (HoFH) is an excellent model for developing in vivo gene therapy in humans. The success of orthotropic liver transplantation in correcting the metabolic abnormalities in HoFH suggests that the correction of low-density lipoprotein receptor (LDLR) expression in hepatocytes via gene therapy should be sufficient for therapeutic efficacy. Vectors based on adeno-associated virus serotype 8 (AAV8) have been previously developed for liver-targeted gene therapy of a number of genetic diseases, including HoFH. In preparation for initiating a Phase 1 clinical trial of AAV8-mediated LDLR gene therapy for HoFH, a combined pharmacology/toxicology study was conducted in a mouse model of HoFH. No dose-limiting toxicities were found at or below 6.0 × 10<sup>13</sup> GC/kg. Therefore, the maximally tolerated dose is greater than the highest dose that was tested. Mild and transient liver pathology was noted at the highest dose. Therefore, the no effect dose was greater than or equal to the middle dose of 7.5 × 10<sup>12</sup> GC/kg. The minimally effective dose was determined to be ≤7.5 × 10<sup>11</sup> GC/kg, based on stable reductions in cholesterol that were considered to be clinically significant. This translates to a therapeutic window of ≥80-fold for the treatment of HoFH.
Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells (2021)

Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.
Anabolic Agents. 2-Methylene-5α-androstane Derivatives (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnabolic Agents. 2-Methylene-5α-androstane DerivativesR. E. Counsell and P. D. KlimstraCite this: J. Med. Chem. 1963, 6, 6, 736–738Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/jm00342a023https://doi.org/10.1021/jm00342a023research-articleACS PublicationsRequest reuse permissionsArticle Views56Altmetric-Citations5LEARN 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
Chemical cascades in water for the synthesis of functionalized aromatics from furfurals (2016)

One-pot synthetic routes from furfurals to aromatic compounds have been developed in water, and the phthalimide products converted to functionalised benzenes.
A simple array platform for microRNA analysis and its application in mouse tissues (2007)

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that regulate gene expression at the post-transcriptional level and play a critical role in many important biological processes. Most miRNAs are conserved between humans and mice, which makes it possible to analyze their expressions with a set of selected array probes. Here, we report a simple array platform that can detect 553 nonredundant miRNAs encompassing the entire set of miRNAs for humans and mice. The platform features carefully selected and designed probes with optimized hybridization parameters. Potential cross-reaction between mature miRNAs and their precursors was investigated. The array platform was used to analyze miRNAs in the mouse central nervous system (CNS, spinal cord and brain), and two other non-CNS organs (liver and heart). Two types of miRNAs, differentially expressed organ/tissue-associated miRNAs and ubiquitously expressed miRNAs, were detected in the array analysis. In addition to the previously reported neuron-related miR-124a, liver-related miR-122a, and muscle-related miR-133a, we also detected new tissue-associated miRNAs (e.g., liver-associated miR-194). Interestingly, while the majority of pre-miRNAs were undetectable, miR690, miR709, and miR720 were clearly detected at both mature and precursor levels by the array analysis, indicating a limited cross-reaction between pre-miRNAs and their mature miRNAs. The reliability of this array technology was validated by comparing the results with independent Northern blot analyses and published data. A new approach of data normalization based on Northern blot analysis of one ubiquitously expressed miRNA is introduced and compared with traditional approaches. We expect this miRNA array platform to be useful for a wide variety of biological studies.
Metrology and Simulation of Chemical Transport in Microchannels (1998)

We are working towards building a CAD tool (NetFlow) for microfluidic systems. To support the development of this tool, diffusion and flow experiments are being performed in microchannels. In this paper, we describe the novel flow visualization approach developed for these experiments and report experimental results and corresponding simulations for fluid transport in microchannels. The experimental approach relies on the use of a caged, charged fluorescent dye which can be activated (uncaged) by a UV laser beam and tracked by fluorescence imaging (1). In contrast to standard methods for inserting a dye plug in a microchannel, this is the only technique which allows definition of very precise regions at any place along the channel. Specifically, this allows a narrow definition of starting plugs and therefore an improved determination of the flow profile. We have used this technique to study diffusion, pressure-driven flow, and electrokinetic flow in various microchannel geometries.
Protein Splicing Involving the Saccharomyces cerevisiae VMA Intein (1996)

Protein splicing involves the excision of an internal protein segment, the intein, from a precursor protein and the concomitant ligation of the flanking N- and C-terminal regions. It occurs in mesophilic bacteria, yeast, and thermophilic archaea. The ability to control protein splicing of a thermophilic intein by temperature and pH in a foreign protein context facilitated the study of the mechanism of protein splicing in thermophiles. On the other hand, no direct studies have been done on the mechanism of protein splicing in mesophiles. We examined the splicing of a chimeric protein containing the intein of the vacuolar ATPase subunit (VMA) of Saccharomyces cerevisiae that involves cysteines rather than serines at the reaction center. The steps in the splicing process were deduced by analyzing intermediates and side products that accumulated as a result of amino acid substitutions and were found to be analogous to those occurring in thermophiles. Moreover, appropriate amino acid replacements allowed us to develop the first mesophilic in vitro protein splicing system as well as strategies for modulating the rate of protein splicing and for converting the splicing reaction to an efficient protein cleavage reaction at either splice junction.
Quantitative analysis of disseminated tumor cells in the bone marrow by automated fluorescence image analysis (2000)

Accurate quantification of disseminated tumor cells in hematological samples is of fundamental importance in clinical oncology. However, even highly standardized protocols allow only a rough estimation of the total analyzed cell number, as sample processing may have adverse effects on the number of cells available for analysis. The fluorescence-based microscopic scanning system (MetaCyte) detects, counts, captures, and relocates immunolabeled tumor cells in hematopoietic samples. We report on a cell-counting approach that has been implemented into the scanning system to precisely quantify the number of cells per slide. The cell-counting function, which was designed to determine the number of all nucleated (DAPI-stained) cells on the slide, allows an accurate counting of the tumor cells and the total number of cells analyzed in the given microscopic sample. The reliability of the cell-counting approach was demonstrated by the analysis of DAPI-stained images with 18-1,363 nucleated cells. A good correlation (r(2) = 0.965) between the manually and automatically gained results was observed. The counting accuracy could even be optimized after implementing a correction factor. To prove or disprove an interslide variation, routine bone marrow cytospin preparations from neuroblastoma patients were immunostained for GD2/FITC and counterstained with DAPI. Automatic cell counting of cytospin preparations from the same patients showed significant differences in the total cell number (up to 67% cell loss during preparation, with a maximum interslide difference of 4.7 x 10(5) mononuclear cells). We conclude that determination of the tumor cell content in hematopoietic samples is only reliable when it is performed together with accurate cell counting.