gebhart/patrepeval huggingface dataset:
Mercaptocalixarene-Capped Gold Nanoparticles via Postsynthetic Modification and Direct Synthesis: Effect of Calixarene Cavity-Metal Interactions (2008)

Evidence for interactions between π-electron-rich calixarene cavities and the surface of gold nanoparticles is demonstrated using a comparative synthetic approach involving the capping of the nanoparticles with thiol ligands. In one approach, thiol ligands are systematically titrated onto existing 5.3 nm gold nanoparticles in solution (postsynthetic synthesis approach), whereas in the other a gold solution is reduced in the presence of thiol ligands (direct synthesis approach). The calixarene cavity is placed in close proximity and facing toward the gold nanoparticle surface upon adsorption of ligand 5,11,17,23-tetrakis-mercaptomethyl-25,26,27,28-tetrapropoxylcalix[4]arene (MMC), which comprises four upper-rim thiol groups. The other two ligands used in this investigation contain either four thiol groups on the calixarene lower-rim, 25,26,27,28-tetrakis(4-mercaptobutyloxy)calix[4]arene (MBC), or a model monodentate thiol, 4-methoxybenzenemethanethiol (MBM), as controls. The orientation of the cavity in MMC is toward the gold surface upon adsorption, which is in complete contrast to its isomer MBC in which the cavity points away from the surface and is located further away. Control ligand MBM lacks a calixarene cavity though still possessing an electron-rich arene ring in close proximity to the gold nanoparticle surface upon adsorption. The surface plasmon resonance absorption (SPR) band red shifts ∼5 nm in wavelength and increases ∼10% in absorption intensity during titration of the gold surface with MMC, as monitored via UV−vis spectroscopy, until the onset of surface site saturation, which corresponds to a molecular footprint of ∼116 Å2 per MMC molecule. Using MBC under identical conditions produces no change in either the SPR band wavelength or absorbance. Adsorption of ligand MBM to the gold nanoparticle surface results in a similar increase as MMC on the SPR absorption intensity and no change in SPR band wavelength. These results can be understood on the basis of interactions between the π-electron-rich calixarene cavity and metal surface. The influence of the calixarene cavity on SPR band wavelength was also observed in nanoparticles prepared by the direct synthesis approach, in which gold reduction occurred in the presence of thiol ligand. The MMC-capped nanoparticles had a higher SPR band wavelength relative to those capped with MBC and MBM. Altogether, these results demonstrate that even for colloids that are relatively large compared with molecular clusters, subtle characteristics of the capping ligand such as the presence of a π-electron rich cavity influence surface microenvironment upon adsorption.
DNA Sequencing by Primer Walking with Strings of Contiguous Hexamers (1992)

When template DNA is saturated with a single-stranded DNA binding protein (SSB), strings of three or four contiguous hexanucleotides (hexamers) can cooperate through base-stacking interactions to prime DNA synthesis specifically from the 3' end of the string. Under the same conditions, priming by individual hexamers is suppressed. Strings of three of four hexamers representing more than 200 of the 4096 possible hexamers primed easily readable sequence ladders at more than 75 different sites in single-stranded or denatured double-stranded templates 6.4 kilobases to 40 kilobase pairs long, with a success rate of 60 to 90 percent. A synthesis of 1 micromole of hexamer supplies enough material for thousands of primings, so multiple libraries of all 4096 hexamers could be distributed at a reasonable cost. Such libraries would allow rapid and economical sequencing. Automating this strategy could increase the speed and efficiency of large-scale DNA sequencing by at least an order of magnitude.
A virus discovery method incorporating DNase treatment and its application to the identification of two bovine parvovirus species (2001)

Identification of previously unrecognized viral agents in serum or plasma samples is of great medical interest but remains a major challenge, primarily because of abundant host DNA. The current methods, library screening or representational difference analysis (RDA), are very laborious and require selected sample sets. We have developed a simple and reproducible method for discovering viruses in single serum samples that is based on DNase treatment of the serum followed by restriction enzyme digestion and sequence-independent single primer amplification (SISPA) of the fragments, and have evaluated its performance on known viruses. Both DNA viruses and RNA viruses at a concentration of approximately 10(6) genome equivalents per ml were reproducibly identified in 50 microl of serum. While evaluating the method, two previously unknown parvoviruses were discovered in the bovine sera used as diluent. The near complete genome sequence of each virus was determined; their classification as two species (provisionally named bovine parvoviruses 2 and 3) was confirmed by phylogenetic analysis. Both viruses were found to be frequent contaminants of commercial bovine serum. DNase treatment of serum samples may prove to be a very useful tool for virus discovery. The DNase-SISPA method is suitable for screening of a large number of samples and also enables rapid sequence determination of high-titer viruses.
Sequences in the 5′ Nontranslated Region of Hepatitis C Virus Required for RNA Replication (2001)

Sequences in the 5' and 3' termini of plus-strand RNA viruses harbor cis-acting elements important for efficient translation and replication. In case of the hepatitis C virus (HCV), a plus-strand RNA virus of the family Flaviviridae, a 341-nucleotide-long nontranslated region (NTR) is located at the 5' end of the genome. This sequence contains an internal ribosome entry site (IRES) that is located downstream of an about 40-nucleotide-long sequence of unknown function. By using our recently developed HCV replicon system, we mapped and characterized the sequences in the 5' NTR required for RNA replication. We show that deletions introduced into the 5' terminal 40 nucleotides abolished RNA replication but only moderately affected translation. By generating a series of replicons with HCV-poliovirus (PV) chimeric 5' NTRs, we could show that the first 125 nucleotides of the HCV genome are essential and sufficient for RNA replication. However, the efficiency could be tremendously increased upon the addition of the complete HCV 5' NTR. These data show that (i) sequences upstream of the HCV IRES are essential for RNA replication, (ii) the first 125 nucleotides of the HCV 5' NTR are sufficient for RNA replication, but such replicon molecules are severely impaired for multiplication, and (iii) high-level HCV replication requires sequences located within the IRES. These data provide the first identification of signals in the 5' NTR of HCV RNA essential for replication of this virus.
Categorizing Biomarkers of the Human Exposome and Developing Metrics for Assessing Environmental Sustainability (2012)

The concept of maintaining environmental sustainability broadly encompasses all human activities that impact the global environment, including the production of energy, use and management of finite resources such as petrochemicals, metals, food production (farmland, fresh and ocean waters), and potable water sources (rivers, lakes, aquifers), as well as preserving the diversity of the surrounding ecosystems. The ultimate concern is how one can manage Spaceship Earth in the long term to sustain the life, health, and welfare of the human species and the planet's flora and fauna. On a more intimate scale, one needs to consider the human interaction with the environment as expressed in the form of the exposome, which is defined as all exogenous and endogenous exposures from conception onward, including exposures from diet, lifestyle, and internal biology, as a quantity of critical interest to disease etiology. Current status and subsequent changes in the measurable components of the exposome, the human biomarkers, could thus conceivably be used to assess the sustainability of the environmental conditions with respect to human health. The basic theory is that a shift away from sustainability will be reflected in outlier measurements of human biomarkers. In this review, the philosophy of long-term environmental sustainability is explored in the context of human biomarker measurements and how empirical data can be collected and interpreted to assess if solutions to existing environmental problems might have unintended consequences. The first part discusses four conventions in the literature for categorizing environmental biomarkers and how different types of biomarker measurements might fit into the various grouping schemes. The second part lays out a sequence of data management strategies to establish statistics and patterns within the exposome that reflect human homeostasis and how changes or perturbations might be interpreted in light of external environmental stressors. The underlying concept is to identify probative outliers from the "unremarkable exposome" in individuals or subpopulations that could be used for discerning deviations from the healthy environment, much like current diagnostic medicine uses batteries of blood and urine tests to screen for preclinical disease conditions. Such empirically derived human in vivo data could subsequently be integrated into high-throughput in vitro and in silico testing of environmental and manufactured chemicals to support real-world toxicity evaluations.
X-ray photoelectron spectroscopy applied to gold-decorated mineral standards of biological interest (1984)

Reproducible high resolution spectra of nonconducting minerals of interest in biological calcification have been obtained by x-ray photoelectron spectroscopy, utilizing a technique we call biased referencing, a combination of gold decoration and electron charge neutralization of the samples. Minerals examined were hydroxyapatite [Ca10(PO4)6(OH)2], fluorapatite [Ca10(PO4)6F2], calcium carbonate (CaCO3), octacalcium phosphate [Ca8H2(PO4)6 ⋅ 5H2O], monetite (CaHPO4), brushite (CaHPO4 ⋅ 2H2O), calcium pyrophosphate (Ca2P2O7), and an amorphous calcium phosphate synthesized at neutral pH (Ca/P=1.47). Samples were pressed into thin wafers onto which a small gold dot was affixed by vacuum deposition. Biased referencing provided calibration of sample core level ionizations (O 1s, Ca 2p, P 2p, F 1s, and C 1s) to the Fermi level of Au 4f7/2 set at a conductive value of 84.0 eV. Measured binding energies represent initial data for these gold-decorated insulators and may be used to compare data similarly generated from mineralized biological tissues.
Psoralen Photobiology: Recent Advances (1996)

Clinical efficacy may arise from psoralen-induced photodamage by the induction of a panoply of biomolecules. In cellular studies with UV or photoactivatable agents, the activation of NF-kappa B, probably the most widely studied transcription factor, occurs after its release from an inhibiting factor, I kappa B. The activation of transcription factors has also been correlated with the UV absorption spectrum of DNA (35). Furthermore, it was shown that the photoadducts do not need to be processed or repaired because transcription factor induction is observed in repair-deficient cells. In these latter cells lower UV doses are required to induce these transcription factors. As a result of transcription factor induction, treated cells may have a greater number of class I molecules on their surface and an altered cytokine profile. It is possible (and likely) that these effects occur in different cells to different extents. The important message is that activational events may occur that could alter the cell's (or cells') ability to regulate a disease process. Many studies have shown that the time frame for this type of damage-induced event may range from seconds to minutes (36). Clearly 8-MOP/UVA-induced events such as those described above could be initiated as the result of a single photochemotherapy session.
Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions (2014)

Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.
14-3-3 Facilitates Insulin-Stimulated Intracellular Trafficking of Insulin Receptor Substrate 1 (2002)

The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. These findings strongly suggest that 14-3-3 participates in the intracellular trafficking of IRS-1 by promoting the displacement of serine-phosphorylated IRS-1 from particular structures. They also suggest that 14-3-3 proteins could play an integral role in the process of insulin desensitization.
Speaker dependent keyword spotting for accessing stored speech (1994)

The DFS and overall survival rates for recurrent OS after contemporary therapy remained poor even for patients with isolated pulmonary recurrence. Therefore, new treatment strategies are needed.
Bacterial synthesis of active rat stearyl-CoA desaturase lacking the 26-residue amino-terminal amino acid sequence. (1988)

Two clones containing inserts in pBR322 that together include the entire 1074-base open reading frame coding for the 358 amino acids of rat liver stearyl-CoA desaturase have been used to construct expression vectors for residues 3-358 and 27-358 fused to the first 6 residues of beta-galactosidase and several amino acids of the multiple cloning site of pUC8. Growth of transformed Escherichia coli under conditions for suppression of the lac promoter, followed by subsequent induction of these cultures results in the synthesis of higher levels of desaturase proteins than those found in induced rat liver. The proteins are almost completely associated with the membrane fraction of cell homogenates. Posttranslational iron insertion into the apoproteins, either in vitro with membrane preparations or by iron addition during induction, results in the formation of active holoenzyme which can be reconstituted with NADH cytochrome b5 reductase and cytochrome b5 to form an active stearyl-CoA desaturase system. The deletion of the first 26 amino-terminal amino acid residues does not affect either enzyme activity or membrane binding. Therefore, the unusual sequence of 11 residues containing 10 amino acids with hydroxyl groups plays no apparent significant role in either protein insertion into membranes or iron chelation. Since the protein product for residues 3-358 is processed even further to delete the initial 33 amino-terminal residues, the limiting polypeptide primary structure required for an active membrane-bound catalyst is even smaller than this initial deletion mutation indicates.
An Efficacious Synthetic Strategy for cis-Clerodane Diterpenoids. Application to the Total Synthesis of (±)-6β-Acetoxy-2-oxokolavenool (2001)

An efficient synthetic strategy for cis-clerodane diterpenoids has been developed. The key ingredient is the face selective Diels-Alder reaction of dienophile 8. The successful application of this strategy has culminated in the total synthesis of the naturally occurring compound 6β-acetoxy-2-oxokolavenool in racemic form.
Recurrent neural networks for language understanding (2013)

Recurrent Neural Network Language Models (RNN-LMs) have recently shown exceptional performance across a variety of applications. In this paper, we modify the architecture to perform Language Understanding, and advance the state-of-the-art for the widely used ATIS dataset. The core of our approach is to take words as input as in a standard RNN-LM, and then to predict slot labels rather than words on the output side. We present several variations that differ in the amount of word context that is used on the input side, and in the use of non-lexical features. Remarkably, our simplest model produces state-of-the-art results, and we advance state-of-the-art through the use of bagof-words, word embedding, named-entity, syntactic, and wordclass features. Analysis indicates that the superior performance is attributable to the task-specific word representations learned by the RNN.
The role of microRNA genes in papillary thyroid carcinoma (2005)

Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was up-regulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the up-regulation (11- to 19-fold) of miR-221, -222, and -146 was strongest showed dramatic loss of KIT transcript and Kit protein. In 5 of 10 such cases, this down expression was associated with germline single-nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation.
Phylogenetic analysis of Japanese encephalitis virus: envelope gene based analysis reveals a fifth genotype, geographic clustering, and multiple introductions of the virus into the Indian subcontinent. (2001)

We report the analysis of the complete nucleotide sequence for the Indian isolate (P20778; Genbank Accession number AF080251) of Japanese encephalitis virus (JEV). The phylogenetic tree topology obtained using thirteen complete genome sequences of JEV was reproduced with the envelope, NS1, NS3, and NS5 genes and revealed extensive divergence between the two Indian strains included. A more exhaustive analysis of JEV evolution using 107 envelope sequences available for isolates from different geographic locations worldwide revealed five distinct genotypes of JEV, displaying a minimum nucleotide divergence of 7% with high bootstrap support values. The tree also revealed overall clustering of strains based on geographic location, as well as multiple introductions of JEV into the Indian subcontinent. Nonsynonymous nucleotide divergence rates of the envelope gene estimated that the ancestor common to all JEV genotypes arose within the last three hundred years.
Evasion of Toll-like receptor 5 by flagellated bacteria (2005)

Toll-like receptor 5 (TLR5) recognizes an evolutionarily conserved site on bacterial flagellin that is required for flagellar filament assembly and motility. The alpha and epsilon Proteobacteria, including the important human pathogens Campylobacter jejuni, Helicobacter pylori, and Bartonella bacilliformis, require flagellar motility to efficiently infect mammalian hosts. In this study, we demonstrate that these bacteria make flagellin molecules that are not recognized by TLR5. We map the site responsible for TLR5 evasion to amino acids 89-96 of the N-terminal D1 domain, which is centrally positioned within the previously defined TLR5 recognition site. Salmonella flagellin is strongly recognized by TLR5, but mutating residues 89-96 to the corresponding H. pylori flaA sequence abolishes TLR5 recognition and also destroys bacterial motility. To preserve bacterial motility, alpha and epsilon Proteobacteria possess compensatory amino acid changes in other regions of the flagellin molecule, and we engineer a mutant form of Salmonella flagellin that evades TLR5 but retains motility. These results suggest that TLR5 evasion is critical for the survival of this subset of bacteria at mucosal sites in animals and raise the intriguing possibility that flagellin receptors provided the selective force to drive the evolution of these unique subclasses of bacterial flagellins.