gebhart/patrepeval huggingface dataset:
Imprinted Polymers as Protecting Groups for Regioselective Modification of Polyfunctional Substrates (1999)

Imprinted polymers were prepared using a functional monomer derived from boronophthalide and a number of steroid templates bearing spatially separated hydroxyl groups. The cooperative nature of the binding interaction was demonstrated in polymers imprinted with androst-5-ene-3β,17β-diol and its structural analogues. The stoichiometry and kinetics of binding were probed using IR spectroscopy, selective solvent extractions, and chemical modification experiments. The feasibility of using imprinted polymers as reusable protecting groups was established by the regioselective acylation of trihydroxysteroids bound to polymers imprinted with structurally related diols. In polymers prepared with tert-butyl ester templates “matched” to the substrate, regioselectivities as high as 23.1:1 (24-acetate:3-acetate) in the monoester products (65% of recovered material) were seen. In the “unmatched” case, the ratio fell to 5.4:1; however, in functionally identical control polymers, imprinted with ethylene glycol, the regioselectivity was completely reversed (<1:100), and only poor yields of monoesters (13%) were obtained.
ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature. (2002)

Physiological differences between tumor and normal vasculature provide a target for drug discovery. In particular, the immature nature of tumor vasculature may render it intrinsically sensitive to disruption by agents affecting the endothelial cell cytoskeleton, including tubulin-binding agents. In this article, we report the synthesis of a water-soluble phosphate prodrug, ZD6126, of the tubulin-binding agent N-acetylcolchinol. In vitro studies demonstrate the comparative tubulin-binding properties of the prodrug and active drug, and show the induction of pronounced, reversible changes in endothelial cell morphology at subcytotoxic doses. Neither ZD6126 nor N-acetylcolchinol showed effects on the growth of human umbilical vein endothelial cells at concentrations below 100 micro M. In contrast, changes in endothelial cell morphology were seen at much lower, noncytotoxic concentrations (0.1 micro M) of ZD6126 and more pronounced effects were seen in proliferating versus confluent endothelial cell cultures. In vivo studies were carried out using a murine tumor model (CaNT) with single administration of a dose well below the maximum tolerated dose. These studies showed a large reduction in vascular volume, induction of extensive necrosis in tumors, and a reduced tumor cell yield in a clonal excision assay, consistent with vascular rather than cytotoxic effects. A viable rim of tumor remained after single-dose administration and minimal growth delay was observed. However, well-tolerated, multiple administration regimens led to pronounced tumor-growth delay. In the human xenograft FaDu, the growth delay given by a single dose of paclitaxel was enhanced by combination with a single dose of ZD6126, and the growth delay given by the combination was greater than the sum of the growth delays from the individual treatments. These findings show that ZD6126 is a promising antivascular agent for the treatment of solid tumors.
Osmotic Loading of Neutralizing Antibodies Demonstrates a Role for Protein-tyrosine Phosphatase 1B in Negative Regulation of the Insulin Action Pathway (1995)

Protein-tyrosine phosphatases (PTPases) have been postulated to balance the steady-state phosphorylation and the activation state of the insulin receptor and its substrate proteins. To explore whether PTP1B, a widely expressed, non-receptor-type PTPase, regulates insulin signaling, we used osmotic shock to load rat KRC-7 hepatoma cells with affinity-purified neutralizing antibodies that immunoprecipitate and inactivate the enzymatic activity of recombinant rat PTP1B in vitro. In cells loaded with PTP1B antibody, insulin-stimulated DNA synthesis and phosphatidylinositol 3'-kinase activity were increased by 42% and 38%, respectively, compared with control cells loaded with preimmune IgG (p < 0.005). In order to characterize the potential site(s) of action of PTP1B in insulin signaling, we also determined that insulin-stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation were increased 2.2- and 2.0-fold, respectively, and that insulin-stimulated receptor kinase activity toward an exogenous peptide substrate was increased by 57% in the PTP1B antibody-loaded cells. Osmotic loading did not alter the cellular content of PTP1B protein, suggesting that the antibody acts in the cell by sterically blocking catalytic interactions between PTP1B and its physiological substrates. These studies demonstrate that PTP1B has a role in the negative regulation of insulin signaling and acts, at least in part, directly at the level of the insulin receptor. These results also show that insulin signaling can be enhanced by the inhibition of specific PTPases, a maneuver that has potential clinical relevance in the treatment of insulin resistance and Type II diabetes mellitus.
Dual-catalyst system to broaden the window of operability in the reduction of nitrogen oxides (NOx) with ammonia (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDual-catalyst system to broaden the window of operability in the reduction of nitrogen oxides (NOx) with ammoniaF. G. Medros, J. W. Eldridge, and J. R. KittrellCite this: Ind. Eng. Chem. Res. 1989, 28, 8, 1171–1177Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/ie00092a009https://doi.org/10.1021/ie00092a009research-articleACS PublicationsRequest reuse permissionsArticle Views75Altmetric-Citations11LEARN 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
Producing Small Domain Features Using Miktoarm Block Copolymers with Large Interaction Parameters (2015)

We demonstrate that small domain features (∼13 nm) can be obtained in a series of polystyrene (PS) and poly(lactic acid) (PLA) block copolymers, PS-(PLA)<sub>2</sub> and (PS)<sub>2</sub>-(PLA)<sub>2</sub>, that combine miktoarm molecular architectures with large interaction parameters. To supplement the experimental work, we used self-consistent field theory in tandem with the random phase approximation to explore and contrast the phase behavior of AB<sub><i>n</i></sub> and A<sub><i>n</i></sub>B<sub><i>n</i></sub> types of miktoarm block copolymers. Specifically, AB<sub>2</sub> and A<sub>2</sub>B<sub>2</sub> were found to be effective molecular architectures for inducing strong shifts in phase boundaries with copolymer composition and to simultaneously tune domain feature sizes. The performance of these systems is markedly different from the corresponding linear diblock copolymers and indicates the potential of macromolecular architecture control for future applications in lithography.
A variable long-precision arithmetic unit design for reconfigurable coprocessor architectures (2002)

This paper presents the organization of an arithmetic unit for variable long-precision (VLP) operands suitable for reconfigurable computing. The reconfigurable arithmetic coprocessor (RAC) cooperates with the host computer in the VLP tasks. The main design issues addressed in the paper are: (a) mapping of the most frequent and time consuming operations of the VLP arithmetic algorithms to RAG, and (b) design of VLP algorithms that allow reduced reconfiguration time between arithmetic operations. The VLP arithmetic algorithms proposed cover multiplication, division and square root. In this paper we present the main building blocks used in the VLP arithmetic circuits, show the similarities of each arithmetic operator and present area/time estimates of these circuits in Xilinx FPGAs.
Substituted 1,8-Naphthyridin-2(1H)-ones Are Superior to Thymine in the Recognition of Adenine in Duplex as Well as Triplex Structures (2002)

The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degrees C (in separate positions) to 3.5 degrees C (in adjacent positions) in PNA-DNA duplexes and from 1.2 degrees C (in separate positions) to 3.2 degrees C (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degrees C when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the end-stacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.
Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies (2015)

Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Relapse, however, remains 1 of the main causes of post-ASCT failure, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in non-transplantation patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation.
Understanding user's query intent with wikipedia (2009)

Understanding the intent behind a user's query can help search engine to automatically route the query to some corresponding vertical search engines to obtain particularly relevant contents, thus, greatly improving user satisfaction. There are three major challenges to the query intent classification problem: (1) Intent representation; (2) Domain coverage and (3) Semantic interpretation. Current approaches to predict the user's intent mainly utilize machine learning techniques. However, it is difficult and often requires many human efforts to meet all these challenges by the statistical machine learning approaches. In this paper, we propose a general methodology to the problem of query intent classification. With very little human effort, our method can discover large quantities of intent concepts by leveraging Wikipedia, one of the best human knowledge base. The Wikipedia concepts are used as the intent representation space, thus, each intent domain is represented as a set of Wikipedia articles and categories. The intent of any input query is identified through mapping the query into the Wikipedia representation space. Compared with previous approaches, our proposed method can achieve much better coverage to classify queries in an intent domain even through the number of seed intent examples is very small. Moreover, the method is very general and can be easily applied to various intent domains. We demonstrate the effectiveness of this method in three different applications, i.e., travel, job, and person name. In each of the three cases, only a couple of seed intent queries are provided. We perform the quantitative evaluations in comparison with two baseline methods, and the experimental results shows that our method significantly outperforms other methods in each intent domain.
n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights (2014)

n-3 Fatty acids (EPA and DHA, from fish oil) are essential fatty acids that are approved for the treatment of severe hypertriacylglycerolaemia and, in some countries, used for reducing the risk of CVD. Because of their inhibitory effects on platelet function, some practitioners have, perhaps unnecessarily, discontinued their use in patients undergoing invasive procedures or being treated with anti-platelet or anticoagulation drugs. Thus, the aim of the present study was to review the effects of n-3 fatty acids on bleeding complications in a wide variety of clinical settings, and to summarise their biochemical mechanism of action in platelet function and coagulation. We surveyed recent publications that either directly studied the effects of n-3 fatty acids on the risk of bleeding or focused on different end-points and also reported the effects on bleeding. n-3 Fatty acid treatment had no effect on the risk of clinically significant bleeding in either monotherapy or combination therapy settings. Although originally believed to operate primarily via the cyclo-oxygenase system, these fatty acids have been shown to affect multiple signalling pathways and thrombotic processes beyond simply affecting platelet aggregation. The present overview found no support for discontinuing the use of n-3 fatty acid treatment before invasive procedures or when given in combination with other agents that affect bleeding. On the contrary, the use of these fatty acids in several settings improved clinical outcomes.
Structural Evidence of a Passive Base-flipping Mechanism for β-Glucosyltransferase (2004)

Beta-glucosyltransferase (BGT) is a DNA-modifying enzyme and a glycosyltransferase. This inverting enzyme transfers glucose from UDP-glucose to the 5-hydroxymethyl cytosine bases of T4 phage DNA. From previous structural analyses we showed that Asp-100 and Asn-70 were, respectively, the catalytic base and the key residue for specific DNA recognition (Larivière, L., Gueguen-Chaignon, V., and Moréra, S. (2003) J. Mol. Biol. 330, 1077-1086). Here, we supply biochemical evidence supporting their essential roles in catalysis. We have also shown previously that BGT uses a base-flipping mechanism to access 5-hydroxymethyl cytosine (Larivière, L., and Moréra, S. (2002) J. Mol. Biol. 324, 483-490). Whether it is an active or a passive process remains unclear, as is the case for all DNA cleaving and modifying enzymes. Here, we report two crystal structures: (i) BGT in complex with a 13-mer DNA containing an A:G mismatch and (ii) BGT in a ternary complex with UDP and an oligonucleotide containing a single central G:C base pair. The binary structure reveals a specific complex with the flipped-out, mismatched adenine exposed to the active site. Unexpectedly, the other structure shows the non-productive binding of an intermediate flipped-out base. Our structural analysis provides clear evidence for a passive process.
Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation (2010)

Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and αvβ1. It was developed by us in the early 90s by a novel procedure, the spatial screening. This strategy resulted in c(RGDfV), the first superactive αvβ3 inhibitor (100 to 1000 times increased activity over the linear reference peptides), which in addition exhibited high selectivity against the platelet receptor αIIbβ3. This cyclic peptide was later modified by N-methylation of one peptide bond to yield an even greater antagonistic activity in c(RGDf(NMe)V). This peptide was then dubbed Cilengitide and is currently developed as drug by the company Merck-Serono (Germany). This article describes the chemical development of Cilengitide, the biochemical background of its activity and a short review about the present clinical trials. The positive anti-angiogenic effects in cancer treatment can be further increased by combination with "classical" anti-cancer therapies. Several clinical trials in this direction are under investigation.
Aqueous Solution Behavior of Anionic Fluorene-co-thiophene-Based Conjugated Polyelectrolytes (2009)

Two anionic fluorene-thiophene alternating copolymers, poly[9,9-bis(4-sulfonylbutoxyphenyl)fluorene-2,7-diyl-2,5-thienylene] (PBS-PFT) and poly[9,9-bis(4-sulfonylbutoxyphenyl)fluorene-2,7-diyl-2,2'-bithiophene-5,5'-diyl] (PBS-PF2T), have been synthesized and their solution behaviors in water studied by UV-vis absorption spectroscopy, fluorescence, and electrical conductivity and compared with that of the previously studied conjugated polyelectrolyte (CPE) poly[9,9-bis(4-sulfonylbutoxyphenyl)fluorene-2,7-diyl-1,4-phenylene] (PBS-PFP). These conjugated polymers do not form solutions at the molecular level in water but instead form clusters. Information on the structure of these clusters for PBS-PF2T comes from small-angle X-ray and neutron scattering. The relative ease of dispersing the copolymers in water increases with an increase in the number of thiophene rings in these alternating copolymers. Semiempirical calculations on the structure suggest that this results from bending of the chains and increased conformational flexibility, decreasing interchain interactions. These CPEs can be dissolved in water at the molecular level using the nonionic surfactants n-dodecylpentaoxyethylene glycol ether (C12E5) or Triton X-100 to obtain systems with increased photoluminescence quantum yield and increased electrical conductivity that can be solution-processed for potential applications as components of sensory or optoelectronic devices.
Escherichia coli Mutants Overproducing Phenylalanyl- and Threonyl-tRNA Synthetase (1979)

The structural genes for threonyl-tRNA synthetase (ThrRS) and phenylalanyl-tRNA synthetase (PheRS) are closely linked on the Escherichia coli chromosome. To study whether these enzymes share a common regulatory element, we have investigated their synthesis in mutants which were selected for overproduction of either ThrRS or PheRS. It was found that mutants isolated previously for overproduction of ThrRS as strains resistant to the antibiotic borrelidin (strains Bor Res 3 and Bor Res 15) did not show an elevated level of PheRS. PheRS-overproducing strains were then isolated as revertants of strains with structurally altered enzymes. Strain S1 is a temperature-resistant derivative of a temperature-sensitive PheRS mutant, and strain G118 is a prototrophic derivative of a PheRS mutant which shows phenylalanine auxotrophy as a consequence of an altered K(m) of this enzyme for the amino acid. In both kinds of revertants, S1 and G118, the concentration of PheRS and ThrRS was increased by factors of about 2.5 and 1.8, respectively, whereas the level of other aminoacyl-tRNA synthetases was not affected by the mutations. Genetic studies showed that the simultaneous overproduction of PheRS and ThrRS in revertants G118 and S1 is based upon gene amplification, since this property was easily lost after growing the cells in the absence of the selective stimulus, and since this loss could be prevented by the presence of the recA allele. By similar criteria, the four- and eightfold overproduction of ThrRS in strains Bor Res 3 and Bor Res 15, respectively, was very stable genetically, indicating that it is caused by a mutational event other than gene amplification. From these results, we conclude that the concomitant increase of PheRS and ThrRS in strains G118 and S1 is an expression of gene duplication and not of a joint regulation of these two aminoacyl-tRNA synthetases. This conclusion is further supported by the result that, in mutant G118 as well as in its parental strain G1, growth in minimal medium lacking phenylalanine led to an additional twofold increase of their PheRS concentration. This increase was restricted to the PheRS, since the level of other aminoacyl-tRNA synthetases, including the ThrRS, stayed unchanged.
Identification of a 27 bp 5′-flanking region element responsible for the low level constitutive expression of the human cytosolic phospholipase A2gene (1995)

The cytosolic phospholipase A2 (cPLA2) gene codes for an enzyme that liberates arachidonic acid from membrane phospholipids, and thus plays a pivotal role in the production of the prostaglandin and leukotriene mediators of inflammation, as well as in a variety of cell signalling pathways. After preliminary studies demonstrated the cPLA2 gene is expressed in a variety of human tissues and was localized to the q arm of chromosome 1 between markers F13B and D1S74, we cloned and characterized the 5'-flanking region of this gene in order to identify the elements controlling its low level constitutive expression. The 5'-flanking region has features typical of a housekeeping gene with no TATA box or CAAT box, although atypical in that it is not GC rich, has no SP1 sites, and has a long run of CA repeats. Analysis of fragments of the 5'-flanking region demonstrated that 541 bp 5' to exon 1 supported reporter gene activity at a level 30% of the SV40 promoter. Interestingly, similar activity was observed by deleting most of the 5'-flanking region down to a 27 bp region containing a sequence with homology to the initiator sequence in the terminal deoxynucleotidyl transferase gene and a polypyrimidine tract similar to the initiator element of the mouse ribosomal protein gene. Within this 27 bp region, a 10 bp fragment (-17 to -8 bp) within the polypyrimidine tract is critical for the baseline expression of the human cPLA2 gene. While the 5'-flanking region contains a putative composite AP-1 and glucocorticoid response element, this region does not respond to tumor necrosis factor-alpha (TNF) and/or glucocorticoids in a cell line (HEp-2) that exhibits upregulation of cPLA2 mRNA transcript levels by TNF. The observations that the expression of the cPLA2 gene is tightly controlled at a relatively low level is consistent with the evolving concept that modulation of expression of this critical enzyme is primarily at the post-translational level.