gebhart/patrepeval huggingface dataset:
Probing the environment of nascent RNA in Escherichia coli transcription elongation complexes utilizing a new fluorescent ribonucleotide analog (1999)

We report the synthesis and characterization of 5-thioacetamidofluorescein-uridine 5'-triphosphate (5-SF-UTP), and its application to the characterization of the environment of the nascent RNA during trans-cription. This analog specifically replaced UTP as a transcription substrate for Escherichia coli and T7 RNA polymerases, and yeast RNA polymerase III. Escherichia coli transcription complexes containing analog incorporated at only position +21 of the RNA were prepared. The RNA was then elongated in the absence of analog, moving the fluorescent group further away from the enzyme active site, and the fluorescence polarization was measured. Analog positioned near the 3' end of the transcript exhibited significantly increased polarization relative to that of free probe, consistent with the constrained environment of the RNA in the DNA-RNA hybrid. Analog positioned 14 nucleotides from the 3' end exhibited significantly decreased polarization relative to that at the 3' end of the RNA, but only slightly above that of free RNA, suggesting that the probe was on the solvent-exposed surface of the polymerase. Molecular modeling of these analog-substituted RNAs produced structures consistent with the experimental data. The excellent substrate properties of this analog make it useful for the characterization of the environment of RNA not only during transcription and translation, but in any type of ribonucleoprotein complex.
Mutational Analysis of β′260–309, a ς70 Binding Site Located on Escherichia coliCore RNA Polymerase (2000)

In eubacteria, the final sigma subunit binds to the core RNA polymerase and directs transcription initiation from any of its cognate set of promoters. Previously, our laboratory defined a region of the beta' subunit that interacts with final sigma(70) in vitro. This region of beta' contained heptad repeat motifs indicative of coiled coils. In this work, we used 10 single point mutations of the predicted coiled coils, located within residues 260-309 of beta', to look at disruption of the final sigma(70)-core interaction. Several of the mutants were defective for binding final sigma(70) in vitro. Of these mutants, three (R275Q, E295K, and A302D) caused cells to be inviable in an in vivo assay in which the mutant beta' is the sole source of beta' subunit for the cell. All of the mutants were able to assemble into the core enzyme; however, R275Q, E295K, A302D were defective for Efinal sigma(70) holoenzyme formation. Several of the mutants were also defective for holoenzyme assembly with various minor final sigma factors. In the recently published crystal structure of Thermus aquaticus core RNA polymerase (Zhang, G., Campbell, E. A., Minakhin, L., Richter, C., Severinov, K. , and Darst, S. A. (1999) Cell 98, 811-824), the region homologous to beta'(260-309) of Escherichia coli forms a coiled coil. Modeling of our mutations onto that coiled coil places the most defective mutations on one face of the coiled coil.
Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes (2003)

The terminally differentiated umbrella cells of bladder epithelium contain unique cytoplasmic organelles, the fusiform vesicles, which deliver preassembled crystalline arrays of uroplakin proteins to the apical cell surface of urothelial umbrella cells. We have investigated the possible role of Rab proteins in this delivery process, and found Rab27b to be expressed at an extraordinary high level (0.1% of total protein) in urothelium, whereas Rab27b levels were greatly reduced (to <5% of normal urothelium) in cultured urothelial cells, which synthesized only small amounts of uroplakins and failed to form fusiform vesicles. Immuno-electron microscopy showed that Rab27b was associated with the cytoplasmic face of the fusiform vesicles, but not with that of the apical plasma membrane. The association of Rab27b with fusiform vesicles and its differentiation-dependent expression suggest that this Rab protein plays a role in regulating the delivery of fusiform vesicles to the apical plasma membrane of umbrella cells.
Large second-order nonlinearity in poled fused silica (1991)

A large second-order nonlinearity [chi((2)) 1 pm/V 0.2 chi((2)) (22) for LiNbO(3)] is induced in the near-surface ( 4 microm) region of commercial fused-silica optical flats by a temperature (250-325 degrees C) and electric-field (E ~ 5 x 10(4) V/cm) poling process. Once formed, the nonlinearity, which is roughly 10(3)-10(4) times larger than that found in fiber second-harmonic experiments, is extremely stable at room temperature and laboratory ambient. The nonlinearity can be cycled by repeated depoling (temperature only) and repoling (temperature and electric field) processes without history effects. Possible mechanisms, including nonlinear moieties and electric-field-induced second-order nonlinearities, are discussed.
Overview of three-dimensional shape measurement using optical methods (2000)

We first provide an overview of 3-D shape measurement us- ing various optical methods. Then we focus on structured light tech- niques where various optical configurations, image acquisition tech- niques, data postprocessing and analysis methods and advantages and limitations are presented. Several industrial application examples are presented. Important areas requiring further R&D are discussed. Finally, a comprehensive bibliography on 3-D shape measurement is included, although it is not intended to be exhaustive. © 2000 Society of Photo-Optical Instrumentation Engineers. (S0091-3286(00)00101-X)
A review of preclinical animal models utilised for TB vaccine evaluation in the context of recent human efficacy data (2013)

There is an urgent need for an improved TB vaccine. Vaccine development is hindered by the lack of immune correlates and uncertain predictive value of preclinical animal models. As data become available from human efficacy trials, there is an opportunity to evaluate the predictive value of the criteria used to select candidate vaccines. Here we review the efficacy in animal models of the MVA85A candidate vaccine in light of recent human efficacy data and propose refinements to the preclinical models with the aim of increasing their predictive value for human efficacy.
Bilateral Ovarian Metastases fromALKRearranged Non-Small Cell Lung Cancer (2014)

Anaplastic lymphoma kinase (ALK) rearrangement, is a kind of driver mutation, accounts for 3%-5% of non-small cell lung cancer (NSCLC). NSCLC patients harboring ALK fusion genes have distinct clinical features and good response to ALK inhibitors. Metastasis from lung cancer to the ovary has rarely been known. We report a case of a 54-year-old woman with bilateral ovarian metastases from ALK rearranged NSCLC. She underwent bilateral salpingo-oophorectomy for ovary masses, which were progressed after cytotoxic chemotherapy although primary lung mass was decreased. Histopathological examination of the ovary tumor showed characteristic adenocarcinoma patterns of the lung and ALK rearrangement.
Microplate assays for high-throughput screening. (1998)

Microplates containing an 8 x 12 array of 96-wells are the most prevalent format for screening compound libraries in high-throughput applications today. These plates are suitable for use in a wide variety of homogeneous and heterogeneous assays to measure binding interactions, enzyme activity and cell proliferation. Assays widely performed in microplates include immunoassays, scintillation counting methods and cell proliferation assays; highly sensitive fluorescence-based assays have recently been introduced for microplate formats. Instrumentation for plate handling and reading assay data in the 96-well format is currently available. Future directions involve assay miniaturization in high density plates and automating the entire screening process.
Molecularly Imprinted Sorbent Assays: Recent Developments and Applications (2009)

Molecular imprinting has attracted considerable attention, because it offers the tantalising prospect of specific antibody-mimicking recognition and binding sites, coupled with several distinct advantages such as excellent stability, ease of preparation and low cost. In this Minireview, recent progress in molecularly imprinted sorbent assays is discussed, with a particular emphasis on the most significant developments and applications over the last few years.
A Quantum‐Dot‐Based Molecular Ruler for Multiplexed Optical Analysis (2010)

Nanoshapes and sizes: A time-resolved multicolor optical analysis of Förster resonance energy transfer (FRET) from a luminescent terbium complex to different semiconductor quantum dots allows the rapid and accurate measurement of the size and shape of different functionalized quantum dots under physiological conditions. This spectroscopic ruler opens the possibility of a simultaneous analysis of different biological processes at sub-nanomolar concentrations. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. 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.
A multiphase series-resonant converter with a new topology and a reduced number of thyristors (1995)

Multiphase series resonant (SR) power converters provide a flexible way to transform power between a utility grid and a multiphase load or source. The current implementations all suffer from a high component count, which makes the use of these power converters unattractive from an economical point of view. A new topology for multiphase SR power converters has been proposed in the literature in a simulation context. This topology uses half the number of power semiconductors compared to the existing multiphase SR power converters. The present paper addresses the implementation of the new topology in a prototype power converter. The old and new topologies are presented. The operation of the new topology is explained. In the new topology the resonant circuit is grounded at one side, which compared to the old topology imposes a restriction on the operation. The paper shows both simulation data and measured waveforms. It is explained that the economical gain due to the reduction in component count is offset by a lower power rating. The paper finishes with conclusions and acknowledgments.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pt‐Al2O3 interfacial bonding in implantable hermetic feedthroughs: Morphology and orientation (2011)

The present work examines the chemistry, microstructure, and crystallography of a Pt-Al(2)O(3) joint used in implantable hermetic feedthrough designs in neural prostheses. Pt was joined to Al(2)O(3) by passing Pt pins through green Al(2)O(3) disks and then sintering in air. This created a Pt-Al(2)O(3) joint that was prepared for the current investigation by gross sectioning and then polishing and sectioning into slices using focused ion beam milling. The slices were examined by scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. Two types of interfaces in the sintered material were identified: Vitreous-bonded Pt-glass-Al(2)O(3) and direct-bonded Pt-Al(2)O(3). In the case of the former, glass formation owing to the presence of glass-forming additives (to enhance densification and suppress grain growth) and consequent wetting of both the Pt and Al(2)O(3) facilitated interfacial bonding. In the case of the latter, the interfacial planes were (002)(Pt) // (022)Al(2)O(3) [rhombohedral] or (002)(Pt) // (022 2)Al(2)O(3) [hexagonal]. The lattice mismatch was calculated to be 11% (based on the calculated d spacings) or 15% (based on the literature d spacings). Both of these suggest the establishment of semicoherent interfaces.
Identification of Chondromodulin I as a Novel Endothelial Cell Growth Inhibitor (1997)

Cartilage is unique among tissues of mesenchymal origin in that it is resistant to vascular invasion due to an intrinsic angiogenic inhibitor. During endochondral bone formation, however, calcified cartilage formed in the center of the cartilaginous bone rudiment allows vascular invasion, which initiates the replacement of cartilage by bone. The transition of cartilage from the angioresistant to the angiogenic status thus plays a key role in bone formation. However, the molecular basis of this phenotypic transition of cartilage has been obscure. We report here purification of an endothelial cell growth inhibitor from a guanidine extract of bovine epiphyseal cartilage. The N-terminal amino acid sequence indicated that the inhibitor was identical to chondromodulin I (ChM-I), a cartilage-specific growth-modulating factor. Purified ChM-I inhibited DNA synthesis and proliferation of vascular endothelial cells as well as tube morphogenesis in vitro. Expression of ChM-I cDNA in COS7 cells indicated that mature ChM-I molecules were secreted from the cells after post-translational modifications and cleavage from the transmembrane precursor at the predicted processing signal. Recombinant ChM-I stimulated DNA synthesis and proteoglycan synthesis of cultured growth plate chondrocytes, but inhibited tube morphogenesis of endothelial cells. In situ hybridization and immunohistochemical studies indicated that ChM-I is specifically expressed in the avascular zone of cartilage in developing bone, but not present in calcifying cartilage. These results suggest a regulatory role of ChM-I in vascular invasion during endochondral bone formation.
Lentivirus-delivered stable gene silencing by RNAi in primary cells (2003)

Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis elegans, but similar techniques have proven difficult to apply to mammalian systems. Although manipulation of the murine genome has led to identification of genes and their function, this approach is laborious, expensive, and often leads to lethal phenotypes. RNA interference (RNAi) is an evolutionarily conserved process of gene silencing that has become a powerful tool for investigating gene function by reverse genetics. Here we describe the delivery of cassettes expressing hairpin RNA targeting green fluorescent protein (GFP) using Moloney leukemia virus-based and lentivirus-based retroviral vectors. Both transformed cell lines and primary dendritic cells, normally refractory to transfection-based gene transfer, demonstrated stable silencing of targeted genes, including the tumor suppressor gene TP53 in normal human fibroblasts. This report demonstrates that both Moloney leukemia virus and lentivirus vector-mediated expression of RNAi can achieve effective, stable gene silencing in diverse biological systems and will assist in elucidating gene functions in numerous cell types including primary cells.
A Bilateral Gynandromorph of the Western Harvester Ant, Pogonomyrmex occidentalis (Hymenoptera: Formicidae) (1986)

Stephen W. Taber, Oscar F. Francke, A Bilateral Gynandromorph of the Western Harvester Ant, Pogonomyrmex occidentalis (Hymenoptera: Formicidae), The Southwestern Naturalist, Vol. 31, No. 2 (May 22, 1986), pp. 274-276
Increase in -lactam-resistant Proteus mirabilis strains due to CTX-M- and CMY-type as well as new VEB- and inhibitor-resistant TEM-type -lactamases (2008)

Twenty-five of 1423 isolates were found to display intermediate or full resistance to co-amoxiclav, cefotaxime or ceftazidime. Seventeen isolates had reduced susceptibility to co-amoxiclav; of these, seven produced TEM-110, eight produced the new TEM-159, one the new TEM-160 and one TEM-1. Five isolates producing TEM-110, TEM-159 or TEM-160 enzymes shared the same PFGE profile. Three isolates produced an ESBL, CTX-M-1, CTX-M-32 and the new variant, VEB-4. Finally, five isolates with an AmpC phenotype produced CMY-2, two with the same PFGE profile. Our data emphasize the diversity of beta-lactamases found in this species.
In Vivo and In Vitro Arginine Methylation of RNA-Binding Proteins (1995)

Heterogenous nuclear ribonucleoproteins (hnRNPs) bind pre-mRNAs and facilitate their processing into mRNAs. Many of the hnRNPs undergo extensive posttranslational modifications including methylation on arginine residues. hnRNPs contain about 65% of the total NG,NG-dimethylarginine found in the cell nucleus. The role of this modification is not known. Here we identify the hnRNPs that are methylated in HeLa cells and demonstrate that most of the pre-mRNA-binding proteins receive this modification. Using recombinant human hnRNP A1 as a substrate, we have partially purified and characterized a protein-arginine N-methyltransferase specific for hnRNPs from HeLa cells. This methyltransferase can methylate the same subset of hnRNPs in vitro as are methylated in vivo. Furthermore, it can also methylate other RNA-binding proteins that contain the RGG motif RNA-binding domain. This activity is evolutionarily conserved from lower eukaryotes to mammals, suggesting that methylation has a significant role in the function of RNA-binding proteins.
Amino Acid Concentrations in Plasma and Urine in Very Low Birth Weight Infants Fed Protein-Unenriched or Human Milk Protein-Enriched Human Milk (1990)

Preprandial plasma and urine amino acid concentrations were measured in 28 growing, very low birth weight, appropriate-for-gestational-age infants randomly assigned to either protein-unenriched (n = 14) or human milk protein-enriched (n = 14) human milk. The two groups of infants had similar birth weights (900 to 1500 g) and gestational ages (26 to 32 weeks). The study was initiated at a mean age of 19 days when the infants tolerated full feeding volumes and lasted for a mean time of 28 days. Mean protein intake values were 2.1 +/- 0.3 and 3.6 +/- 0.3 g/kg per day (mean +/- SD) and weight gain values were 26.6 +/- 7.4 and 35.1 +/- 3.6 g/day in the protein-unenriched and the protein-enriched groups of infants, respectively. Human milk protein enrichment resulted in significantly increased concentrations of all plasma amino acids except serine, taurine, and histidine. Most urine amino acid concentrations correlated with protein intake and with the plasma concentrations, suggesting that the effects of protein quality and quantity can be evaluated by measuring urinary amino acid concentrations alone, thereby making such studies less invasive. Infants fed protein-unenriched human milk had growth rates below the estimated intrauterine rate as well as low plasma and urine amino acid concentrations, indicating suboptimal protein intake levels. When the plasma concentrations of the essential amino acids in the protein-enriched infants from the present study were compared with concentrations found in the literature in fetal and umbilical cord plasma, both were found to be much higher.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of Residue Phe225 in the Cofactor-Mediated, Allosteric Regulation of the Serine Protease Coagulation Factor VIIa (2000)

Functional regulation by cofactors is fundamentally important for the highly ordered, consecutive activation of the coagulation cascade. The initiating protease of the coagulation system, factor VIIa (VIIa), retains zymogen-like features after proteolytic cleavage of the activating Arg(15)-Ile(16) peptide bond and requires the binding of the cofactor tissue factor (TF) to stabilize the protease domain in an active enzyme conformation. Structural comparison of TF-bound and free VIIa failed to provide a conclusive mechanism for this catalytic activation. This study provides novel insight into the cofactor-dependent regulation of VIIa by demonstrating that the side chain of Phe(225), an aromatic residue that is common to allosterically regulated serine proteases, is necessary for optimal TF-mediated activation of VIIa's catalytic function. However, mutation of Phe(225) did not abolish the cofactor-induced stabilization of the Ile(16)-Asp(194) salt bridge, previously considered the primary switch mechanism for activating VIIa. Moreover, mutation of other residue side chains in the VIIa protease domain resulted in a reduced level of or no stabilization of the amino-terminal insertion site upon TF binding, with little or no effect on the TF-mediated enhancement of catalysis. This study thus establishes a crucial role for the aromatic Phe(225) residue position in the allosteric network that transmits the activating switch from the cofactor interface to the catalytic cleft, providing insight into the highly specific conformational linkages that regulate serine protease function.
Sparse Multipath Channels: Modeling and Estimation (2009)

Multipath signal propagation is the defining characteristic of terrestrial wireless channels. Virtually all existing statistical models for wireless channels are implicitly based on the assumption of rich multipath, which can be traced back to the seminal works of Bello and Kennedy on the wide-sense stationary uncorrelated scattering model, and more recently to the i.i.d. model for multi-antenna channels proposed by Telatar, and Foschini Gans. However, physical arguments and growing experimental evidence suggest that physical channels encountered in practice exhibit a sparse multipath structure that gets more pronounced as the signal space dimension gets large (e.g., due to large bandwidth or large number of antennas). In this paper, we formalize the notion of multipath sparsity and discuss applications of the emerging theory of compressed sensing for efficient estimation of sparse multipath channels.
ANTIBIOTICS SYNTHESIZED BY POSTTRANSLATIONAL MODIFICATION (1993)

Peptides that have antimicrobial activity are synthesized by many prokaryotic and eukaryotic organisms. Antimicrobial peptides commonly contain unusual amino acids that contribute to their properties and functions. Although bacteria synthesize most of these peptides by nonribosomal mechanisms, this review focuses on those that are synthesized by pathways that involve posttranslational modification of ribosomally synthesized precursor peptides. A particularly interesting class of these antimicrobial peptides is the lantibiotics, of which nisin and subtilin are the longest-known examples, although nearly a dozen new lantibiotics have been discovered in recent years. The fact that the lantibiotic structures are derived from gene-encoded peptides means that structural analogs of natural lantibiotics can be constructed by mutagenesis of their structural genes. Recent advances in our understanding of the molecular genetics of lantibiotics has made the construction of novel lantibiotics with enhanced chemical and antimicrobial properties possible. This review describes these advances and proposes future trends of research, as well as potential application of engineered lantibiotics, in the context of the general field of antimicrobial peptides.