gebhart/patrepeval huggingface dataset:
Nucleosides and Nucleotides. 156. Chelation-Controlled and Nonchelation-Controlled Diastereofacial Selective Thiophenol Addition Reactions at the 2‘-Position of 2‘-[(Alkoxycarbonyl)methylene]-2‘-deoxyuridines:  Conversion of (Z)-2‘-[(Alkoxycarbonyl)methylene]-2‘-deoxyuridines into Their (E)-Isomers1 (1997)

The Wittig reaction of 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-beta-D-erythro-pentofuranos-2-ulosyl]uracil (4) with Ph(3)P=CHCO(2)R (R = ethyl or tert-butyl) exclusively gave (Z)-2'-[(alkoxycarbonyl)methylene] derivatives 5 and 13, respectively, in high yields. An unusual beta-facial selectivity of thiophenol addition to the 2'-[(alkoxycarbonyl)methylene] moiety of 5 and 13 was observed, and this facial selectivity was found to be influenced by both the thiolate counter cation and the bulkiness of the alkoxy moiety. Treatment of 2'-[(ethoxycarbonyl)methylene] derivative 5with LiSPh (1.5 equiv) in the presence of PhSH in THF selectively gave 2'beta-(phenylthio) derivative 11 in high yield along with a trace of 2'alpha-(phenylthio) derivative 10. On the other hand, when 2'-[(tert-butoxycarbonyl)methylene] derivative13 was treated with KSPh in the presence of PhSH in dioxane/DMF, the facial selectivity was reversed to selectively give the 2'alpha-(phenylthio) adduct14 (alpha:beta, 77:23) in 90% yield. Oxidation of 14 with m-chloroperbenzoic acid in CH(2)Cl(2) and subsequent pyrolysis of the resulting sulfoxides exclusively gave the (Z)-isomer 13 in 92% yield. The oxidativesyn-elimination of the (2'R)-2'-[(tert-butoxycarbonyl)methyl]-2'-deoxy-2'-thiophenoxy-5'-O-(triisopropylsilyl)uridine (17), which was obtained from 14 in two steps, exclusively gave the desired (E)-[(tert-butoxycarbonyl)methylene] derivatives 18 in 90% yield. Deprotection of 18 gave the (E)-(carboxymethylene)-2'-deoxyuridine (3). The (Z)-(carboxymethylene)-2'-deoxyuridine (2) was synthesized from 13 in a similar manner.
Fructosamine Test-Plus, a modified fructosamine assay evaluated (1991)

We have evaluated Fructosamine Test-Plus, a commercial fructosamine assay based on the reduction of nitro-blue tetrazolium dye in alkaline buffer (Clin Chem 1985;31:1550-4), modified by including a detergent and uricase in the reagent, by changing the concentrations of buffer and dye, and by changing the approach to primary calibration. Specimens were from 2321 participants in a health screening survey in a local workforce. Compared with the original fructosamine method, the Fructosamine Test-Plus method was less affected by protein concentration in the sample and less subject to interference from hyperlipidemia. The changes have also extended the linearity of the assay in the pathological range. However, as a screening method for diabetes mellitus in a population with a disease prevalence of 2.28%, the performance of Fructosamine Test-Plus was similar to the original assay.
Heat Shock Protein–Peptide and HSP-Based Immunotherapies for the Treatment of Cancer (2016)

Intracellular residing heat shock proteins (HSPs) with a molecular weight of approximately 70 and 90 kDa function as molecular chaperones that assist folding/unfolding and transport of proteins across membranes and prevent protein aggregation after environmental stress. In contrast to normal cells, tumor cells have higher cytosolic heat shock protein 70 and Hsp90 levels, which contribute to tumor cell propagation, metastasis, and protection against apoptosis. In addition to their intracellular chaperoning functions, extracellular localized and membrane-bound HSPs have been found to play key roles in eliciting antitumor immune responses by acting as carriers for tumor-derived immunogenic peptides, as adjuvants for antigen presentation, or as targets for the innate immune system. The interaction of HSP-peptide complexes or peptide-free HSPs with receptors on antigen-presenting cells promotes the maturation of dendritic cells, results in an upregulation of major histocompatibility complex class I and class II molecules, induces secretion of pro- and anti-inflammatory cytokines, chemokines, and immune modulatory nitric oxides, and thus integrates adaptive and innate immune phenomena. Herein, we aim to recapitulate the history and current status of HSP-based immunotherapies and vaccination strategies in the treatment of cancer.
Compartmental memory management in a modern web browser (2011)

Since their inception, the usage pattern of web browsers has changed substantially. Rather than sequentially navigating static web sites, modern web browsers often manage a large number of simultaneous tabs displaying dynamic web content, each of which might be running a substantial amount of client-side JavaScript code. This environment introduced a new degree of parallelism that was not fully embraced by the underlying JavaScript virtual machine architecture. We propose a novel abstraction for multiple disjoint JavaScript heaps, which we call compartments. We use the notion of document origin to cluster objects into separate compartments.Objects within a compartment can reference each other directly. Objects across compartments can only reference each other through wrappers. Our approach reduces garbage collection pause times by permitting collection of sub-heaps (compartments), and we can use cross-compartment wrappers to enforce cross origin object access policy.
Monte Carlo reptation model of gel electrophoresis: Steady state behavior (1990)

We study the effect of tube length fluctuations on the mobility and orientation of DNA fragments during continuous field gel electrophoresis, using a Monte Carlo lattice simulation. The variation of mobility with molecular weight is found to be similar to that derived from models that assume a fixed tube length; in particular, the prediction of band inversion still applies. The dependence on field strength is substantially different, however. The mobility initially rises more rapidly with increasing field, but reaches a plateau at a much lower value. In contradiction to models that neglect fluctuations, but in agreement with experimental observations, the steady state orientation of the tube continues to increase after the mobility has saturated and the degree of alignment has a marked dependence on chain length. We discuss how these differences arise from alterations in the tube configuration caused by length fluctuations.
β-deuterium kinetic isotope effects in the purine nucleoside phosphorylase reaction (1991)

1. [2'-2H]Inosine was made from inosine by tetraisopropyldisiloxanyl protection of the 3'- and 5'-positions, oxidation with dimethyl sulphoxide and acetic anhydride, immediate NaB2H4 reduction of the oxo sugar product and inversion at C-2' of the resultant protected [2'-2H]arabino-inosine by trifluoromethanesulphonylation and reaction with caesium propionate, followed by deprotection. 2. The equilibrium-perturbation technique was used to measure beta 2H(V/K) for phosphorolysis of this compound by the purine nucleoside phosphorylase of Escherichia coli as a function of pH. 3. The pH variation indicates an intrinsic effect of 1.068 masked by isotopically silent steps near the pH optimum. 4. The similar pH variation of these beta-deuterium effects and the alpha-deuterium effects measured previously [Stein & Cordes (1981) J. Biol. Chem. 256, 767-772; Lehikoinen, Sinnott & Krenitsky (1989) Biochem. J. 257, 355-359] for this reaction provides the first experimental reassurance for the common assumption that pH changes merely mask and unmask the chemical steps in an enzyme-catalysed reaction, and do not detectably alter transition-state structure. 5. The dihedral angle between the C-H-2' bond and the electron-deficient p-orbital at the transition state is in the range 32-48 degrees, in accord with an essentially planar furanose ring.
Left-handed electromagnetism obtained via nanostructured metamaterials: comparison with that from microstructured photonic crystals (2005)

International audience
DNA-Templated Construction of Copper Nanowires (2003)

We have developed a method to deposit Cu metal onto surface-attached DNA, forming nanowirelike structures that are ∼3 nm tall. DNA is first aligned on a silicon surface and then treated with aqueous Cu(NO3)2. After the copper(II) has electrostatically associated with the DNA, it is reduced by ascorbic acid to form a metallic copper sheath around the DNA. The resulting nanostructures have been observed and characterized by atomic force microscopy. A more complete coating can be obtained by repeating the Cu(II) and ascorbic acid treatment. Control experiments involving treatments with aqueous solutions containing either NO3- or the divalent cation Mg2+ show no change in DNA height upon ascorbic acid exposure. These experiments indicate that copper nanowires, which may be valuable as interconnects in nanoscale integrated circuitry, can be readily generated from DNA molecules on surfaces.
High-level expression, purification, and enzymatic characterization of full-length Thermus aquaticus DNA polymerase and a truncated form deficient in 5' to 3' exonuclease activity. (1993)

The Thermus aquaticus DNA polymerase I (Taq Pol I) gene was cloned into a plasmid expression vector that utilizes the strong bacteriophage lambda PL promoter. A truncated form of Taq Pol I was also constructed. The two constructs made it possible to compare the full-length 832-amino-acid Taq Pol I and a deletion derivative encoding a 544-amino-acid translation product, the Stoffel fragment. Upon heat induction, the 832-amino-acid construct produced 1-2% of total protein as Taq Pol I. The induced 544-amino-acid construct produced 3% of total protein as Stoffel fragment. Enzyme purification included cell lysis, heat treatment followed by Polymin P precipitation of nucleic acids, phenyl sepharose column chromatography, and heparin-Sepharose column chromatography. For full-length 94-kD Taq Pol I, yield was 3.26 x 10(7) units of activity from 165 grams wet weight cell paste. For the 61-kD Taq Pol I Stoffel fragment, the yield was 1.03 x 10(6) units of activity from 15.6 grams wet weight cell paste. The two enzymes have maximal activity at 75 degrees C to 80 degrees C, 2-4 mM MgCl2 and 10-55 mM KCl. The nature of the substrate determines the precise conditions for maximal enzyme activity. For both proteins, MgCl2 is the preferred cofactor compared to MnCl2, CoCl2, and NiCl2. The full-length Taq Pol I has an activity half-life of 9 min at 97.5 degrees C. The Stoffel fragment has a half-life of 21 min at 97.5 degrees C. Taq Pol I contains a polymerization-dependent 5' to 3' exonuclease activity whereas the Stoffel fragment, deleted for the 5' to 3' exonuclease domain, does not possess that activity. A comparison is made among thermostable DNA polymerases that have been characterized; specific activities of 292,000 units/mg for Taq Pol I and 369,000 units/mg for the Stoffel fragment are the highest reported.
Duplicate Maize Wrinkled1 Transcription Factors Activate Target Genes Involved in Seed Oil Biosynthesis (2011)

WRINKLED1 (WRI1), a key regulator of seed oil biosynthesis in Arabidopsis (Arabidopsis thaliana), was duplicated during the genome amplification of the cereal ancestor genome 90 million years ago. Both maize (Zea mays) coorthologs ZmWri1a and ZmWri1b show a strong transcriptional induction during the early filling stage of the embryo and complement the reduced fatty acid content of Arabidopsis wri1-4 seeds, suggesting conservation of molecular function. Overexpression of ZmWri1a not only increases the fatty acid content of the mature maize grain but also the content of certain amino acids, of several compounds involved in amino acid biosynthesis, and of two intermediates of the tricarboxylic acid cycle. Transcriptomic experiments identified 18 putative target genes of this transcription factor, 12 of which contain in their upstream regions an AW box, the cis-element bound by AtWRI1. In addition to functions related to late glycolysis and fatty acid biosynthesis in plastids, the target genes also have functions related to coenzyme A biosynthesis in mitochondria and the production of glycerol backbones for triacylglycerol biosynthesis in the cytoplasm. Interestingly, the higher seed oil content in ZmWri1a overexpression lines is not accompanied by a reduction in starch, thus opening possibilities for the use of the transgenic maize lines in breeding programs.
Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population (2013)

Cytosine DNA methylation is one avenue for passing information through cell divisions. Here, we present epigenomic analyses of soybean recombinant inbred lines (RILs) and their parents. Identification of differentially methylated regions (DMRs) revealed that DMRs mostly cosegregated with the genotype from which they were derived, but examples of the uncoupling of genotype and epigenotype were identified. Linkage mapping of methylation states assessed from whole-genome bisulfite sequencing of 83 RILs uncovered widespread evidence for local methylQTL. This epigenomics approach provides a comprehensive study of the patterns and heritability of methylation variants in a complex genetic population over multiple generations, paving the way for understanding how methylation variants contribute to phenotypic variation.
STEVIOSIDE AS A REPLACEMENT OF SUCROSE IN PEACH JUICE: SENSORY EVALUATION (2001)

ABSTRACT The suitability of stevioside as a sweetener in peach juice was investigated. Comparison between stevioside and sucrose in terms of sweetness, sweet and bitter aftertastes were determined both in water and peach juice. The results demonstrated that 160 mg/L of stevioside may replace 34 g/L of sucrose in juice, with a 25% decrease in calories, without affecting the sensory characteristics of the product. Synergistic and inhibitory effects between sucrose and stevioside were also monitored at different stevioside concentration. A new juice formulation sweetened with a binary mixture of stevioside (160 mg/L) and sucrose (56 g/L) was not significantly different in terms of desirability from a reference product sweetened with 9% sucrose.
Cyanoacetanilides Intermediates in Heterocyclic Synthesis. Part 1: A Facile Synthesis of Polysubstituted and Condensed Pyridones (2004)

Abstract Polysubstituted pyridone derivatives were obtained through interaction of cyanoacetanilides with different reagents such as chalcones, 1,1,3‐tricyano‐2‐aminopropene, and arylidenemalononitrile and acetyl‐acetone.
Size-Dependent Lithium Miscibility Gap in Nanoscale Li[sub 1−x]FePO[sub 4] (2007)

Olivine compounds have emerged as important and enabling positive electrode materials for high-power, safe, long-life lithium rechargeable batteries. In this work, the miscibility gap in undoped is shown to contract systematically with decreasing particle size in the nanoscale regime and with increasing temperature at a constant particle size. These effects suggest that the miscibility gap completely disappears below a critical size. In the size-dependent regime, the kinetic response of nanoscale olivines should deviate from the simple size-scaling implicit in Fickian diffusion.
Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated recruitment of inflammatory macrophages into adipose tissue (2011)

Infiltration of inflammatory macrophages into adipose tissues with the progression of obesity triggers insulin resistance and obesity-related metabolic diseases. We recently reported that macrophage-derived apoptosis inhibitor of macrophage (AIM) protein is increased in blood in line with obesity progression and is incorporated into adipocytes, thereby inducing lipolysis in adipose tissue. Here we show that such a response is required for the recruitment of adipose tissue macrophages. In vitro, AIM-dependent lipolysis induced an efflux of palmitic and stearic acids from 3T3-L1 adipocytes, thereby stimulating chemokine production in adipocytes via activation of toll-like receptor 4 (TLR4). In vivo administration of recombinant AIM to TLR4-deficient (TLR4(-/-)) mice resulted in induction of lipolysis without chemokine production in adipose tissues. Consistently, mRNA levels for the chemokines that affect macrophages were far lower in AIM-deficient (AIM(-/-)) than in wild-type (AIM(+/+)) obese adipose tissue. This reduction in chemokine production resulted in a marked prevention of inflammatory macrophage infiltration into adipose tissue in obese AIM(-/-) mice, although these mice showed more advanced obesity than AIM(+/+) mice on a high-fat diet. Diminished macrophage infiltration resulted in decreased inflammation locally and systemically in obese AIM(-/-) mice, thereby protecting them from insulin resistance and glucose intolerance. These results indicate that the increase in blood AIM is a critical event for the initiation of macrophage recruitment into adipose tissue, which is followed by insulin resistance. Thus, AIM suppression might be therapeutically applicable for the prevention of obesity-related metabolic disorders.
The creation of a novel fluorescent protein by guided consensus engineering (2007)

Consensus engineering has been used to increase the stability of a number of different proteins, either by creating consensus proteins from scratch or by modifying existing proteins so that their sequences more closely match a consensus sequence. In this paper we describe the first application of consensus engineering to the ab initio creation of a novel fluorescent protein. This was based on the alignment of 31 fluorescent proteins with >62% homology to monomeric Azami green (mAG) protein, and used the sequence of mAG to guide amino acid selection at positions of ambiguity. This consensus green protein is extremely well expressed, monomeric and fluorescent with red shifted absorption and emission characteristics compared to mAG. Although slightly less stable than mAG, it is better expressed and brighter under the excitation conditions typically used in single molecule fluorescence spectroscopy or confocal microscopy. This study illustrates the power of consensus engineering to create stable proteins using the subtle information embedded in the alignment of similar proteins and shows that the benefits of this approach may extend beyond stability.
Expression of nestin in the podocytes of normal and diseased human kidneys (2007)

The complex cyto-architecture of the podocyte is critical for glomerular permselectivity. The present study characterizes the expression of nestin, an intermediate filament protein, in human kidneys. In normal kidneys, nestin was detected at the periphery of glomerular capillary loops. Colabeling showed nestin was expressed in WT1-positive cells. Within the podocyte, nestin immunoreactivity was present in the cell body and primary process. This was supported by immunoelectron microscopy. Nestin also colocalized with vimentin in the periphery of capillary loops but not in the mesangium. Nestin was not detected in other structures of the adult human kidney. To determine the potential role of nestin in proteinuria, nestin was examined in kidney biopsies from patients with or without proteinuria. These patients were diagnosed with IgA nephropathy with mild mesangial expansion but without proteinuria, IgA nephropathy with proteinuria, membranous nephropathy (MN), and focal segmental glomerular sclerosis (FSGS). The distribution of nestin in these biopsies was similar to that in the normal kidney. Semiquantitative analysis of immunostaining showed that glomerular nestin expression in IgA nephropathy without proteinuria was not different from normal kidney; however, nestin expression in kidneys of patients with IgA nephropathy and proteinuria, or MN and FSGS with proteinuria was significantly reduced compared with normal kidney (P < 0.01). Reduced nestin mRNA expression in the patients with IgA nephropathy with proteinuria and FSGN was also observed by quantitative real-time PCR. These studies suggest that nestin may play an important role in maintaining normal podocyte function in the human kidney.
Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. (1988)

Human neutrophil (PMN) attachment to human umbilical vein endothelial cells (HUVEC) was evaluated in vitro using two MAbs, R6-5-D6 and RR1/1, that recognize intercellular adhesion molecule-1 (ICAM-1), and one MAb, TS1/18, that recognizes CD18. Pretreatment of the HUVEC with anti-ICAM-1 MAbs produced greater than 50% inhibition of attachment to HUVEC, and IL-1 (0.5 U/ml)- or lipopolysaccharide (LPS) (10 ng/ml)-stimulated HUVEC, and greater than 99% inhibition of f-Met-Leu-Phe (0.5 nM) enhanced adherence. Anti-ICAM-1 MAbs also inhibited by greater than 85% the transendothelial migration induced by 4-h IL-1 (0.5 U/ml) and LPS (10 ng/ml) activation of the HUVEC. That these effects involved a CD18-dependent mechanism is supported by the following results: pretreatment of PMN with TS1/18 produced the same degree of inhibition of attachment and migration as seen with R6-5-D6. In addition, the use of both MAbs together did not further increase the inhibition of cell attachment to stimulated HUVEC. The attachment of PMN from patients with CD18 deficiency to stimulated HUVEC was not reduced by R6-5-D6, and both R6-5-D6 and TS1/18 revealed the same time course for appearance and disappearance of an adherence component on stimulated HUVEC not blocked by either MAb. These results demonstrate that attachment and transendothelial migration of PMN in vitro depend substantially on both CD18 on the PMN and ICAM-1 on the endothelial cell.
Dictyostelium myosin II mechanochemistry promotes active behavior of the cortex on long time scales (2006)

Cell cortices rearrange dynamically to complete cytokinesis, crawlin response to chemoattractant, build tissues, and make neuronal connections. Highly enriched in the cell cortex, actin, myosin II, and actin crosslinkers facilitate cortical movements. Because cortical behavior is the consequence of nanoscale biochemical events, it is essential to probe the cortex at this level. Here, we use high-resolution laser-based particle tracking to examine how myosin II mechanochemistry and dynacortin-mediated actin crosslinking control cortex dynamics in Dictyostelium. Consistent with its low duty ratio, myosin II does not directly drive active bead motility. Instead, myosin II and dynacortin antagonistically regulate other active processes in the living cortex.
Synthesis, Structure, and Reactivity of Cationic Ruthenium(II) Carbene Complexes with Bulky Chelating Bisphosphines:  Design of Highly Active Ring Opening Metathesis Polymerization (ROMP) Catalysts (2004)

Complexes of the type [{(t-Bu)2P(CH2)nP(t-Bu)2-κ2P}XRuCHR]2(Y)2 have been prepared and characterized in solution as well as in the solid state. Parameters governing the ring opening metathesis polymerization (ROMP) activity of these highly active ruthenium catalysts in solution have been assessed. Especially, chloro-bridged dinuclear dicationic ruthenium carbenes with a bis(di-tert-butylphosphino)methane ligand and weakly coordinating or noncoordinating anions display extremely high ROMP activity. Comparison of the solution-phase reactivity reported here with high throughput screening results from gas-phase experiments provide further mechanistic insight into the metathesis reaction with these compounds.
Fast Alpha Nucleophiles: Structures that Undergo Rapid Hydrazone/Oxime Formation at Neutral pH (2014)

Hydrazones and oximes are widely useful structures for conjugate formation in chemistry and biology, but their formation can be slow at neutral pH. Kinetics studies were performed for a range of structurally varied hydrazines, and a surprisingly large variation in reaction rate was observed. Structures that undergo especially rapid reactions were identified, enabling reaction rates that rival orthogonal cycloaddition-based conjugation chemistries.