gebhart/patrepeval huggingface dataset:
Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides (1988)

A series of 3-(substituted thio)-2-hydroxypropionanilides and some corresponding sulfones and sulfoxides of general structure 7, in which R' is methyl or trifluoromethyl, were prepared and tested for antiandrogen activity. Members of the trifluoromethyl series (7, R' = CF3) generally exhibited partial androgen agonist activity whereas the members of the methyl series (7, R' = CH3) were pure antagonists. Lead optimization in the methyl series has led to the discovery of novel, potent antiandrogens, which are peripherally selective. One of these, (RS)-4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'- (trifluoromethyl)propionanilide, 40 (ICI 176334), is being developed currently for the treatment of androgen-responsive benign and malignant disease.
Multimodal Biomedical Imaging with Asymmetric Single-Walled Carbon Nanotube/Iron Oxide Nanoparticle Complexes (2007)

Magnetic iron oxide nanoparticles and near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWNT) form heterostructured complexes that can be utilized as multimodal bioimaging agents. Fe catalyst-grown SWNT were individually dispersed in aqueous solution via encapsulation by oligonucleotides with the sequence d(GT)15, and enriched using a 0.5 T magnetic array. The resulting nanotube complexes show distinct NIR fluorescence, Raman scattering, and visible/NIR absorbance features, corresponding to the various nanotube species. AFM and cryo-TEM images show DNA-encapsulated complexes composed of a approximately 3 nm particle attached to a carbon nanotube on one end. X-ray diffraction (XRD) and superconducting quantum interference device (SQUID) measurements reveal that the nanoparticles are primarily Fe2O3 and superparamagnetic. The Fe2O3 particle-enriched nanotube solution has a magnetic particle content of approximately 35 wt %, a magnetization saturation of approximately 56 emu/g, and a magnetic relaxation time scale ratio (T1/T2) of approximately 12. These complexes have a longer spin-spin relaxation time (T2 approximately 164 ms) than typical ferromagnetic particles due to the smaller size of their magnetic component while still retaining SWNT optical signatures. Macrophage cells that engulf the DNA-wrapped complexes were imaged using magnetic resonance imaging (MRI) and NIR mapping, demonstrating that these multifunctional nanostructures could potentially be useful in multimodal biomedical imaging.
Rendering Schrock‐type Molybdenum Alkylidene Complexes Air Stable: User‐Friendly Precatalysts for Alkene Metathesis (2011)

A matter of convenience: Schrock molybdenum alkylidenes are amongst the most powerful olefin metathesis catalysts known to date, but their sensitivity to air and moisture mandates their handling in a glove-box or by Schlenk techniques. This inconvenience is circumvented by using the corresponding phenanthroline- or bipyridine adducts, which are bench-stable and hence very user-friendly. The active species can be liberated from these precatalysts in uncompromised form on treatment with ZnCl2 in toluene (see scheme). 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.
Structure and function of the CC chemokine receptor (CCR) 8. (2000)

The CC chemokine receptor (CCR) 8 belongs to the seven transmembrane-spanning receptor family and functionally responds to the eukaryotic CC chemokines I-309, thymus and activation-regulated chemokine, macrophage inflammatory protein-1 beta (MIP-1b) and to the products viral MIP-I and viral MIP-II of the Kaposi-associated herpesvirus (HHV-8). Although it has not yet been fully characterised, its restricted expression to lymphoid tissues, i.e. thymus, spleen and lymph nodes, and its abundant up-regulation in Th2 lymphocytes suggest a potential role in lymphocyte activation, migration and differentiation and in allergic diseases. In this article we review the data known up to now related to CCR8 from cloning to protein structure, expression patterns and functional activation by its agonists.
Isolation and Use of a Homologous Histone H4 Promoter and a Ribosomal DNA Region in a Transformation Vector for the Oil-Producing FungusMortierella alpina (2000)

Mortierella alpina was transformed successfully to hygromycin B resistance by using a homologous histone H4 promoter to drive gene expression and a homologous ribosomal DNA region to promote chromosomal integration. This is the first description of transformation in this commercially important oleaginous organism. Two pairs of histone H3 and H4 genes were isolated from this fungus. Each pair consisted of one histone H3 gene and one histone H4 gene, transcribed divergently from an intergenic promoter region. The pairs of encoded histone H3 or H4 proteins were identical in amino acid sequence. At the DNA level, each histone H3 or H4 open reading frame showed 97 to 99% identity to its counterpart but the noncoding regions had little sequence identity. Unlike the histone genes from other filamentous fungi, all four M. alpina genes lacked introns. During normal vegetative growth, transcripts from the two histone H4 genes were produced at approximately the same level, indicating that either histone H4 promoter could be used in transformation vectors. The generation of stable, hygromycin B-resistant transformants required the incorporation of a homologous ribosomal DNA region into the transformation vector to promote chromosomal integration.
Mechanisms of drug‐induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo (1997)

The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.
Handle with care: targeting neutrophils in chronic obstructive pulmonary disease and severe asthma? (2006)

Neutrophils play an important role in the pathogenesis of airway inflammation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Currently available drugs have only limited effects on neutrophilic airway inflammation, particularily in COPD. Therefore, great efforts are undertaken to address neutrophilic inflammation in chronic respiratory disorders, in particular COPD. This review summarizes the rationale for anti-neutrophilic treatment in COPD and asthma and gives a critical overview of current developments in drug therapy. Moreover, unanswered questions and limitations of clinical trial design and choice of outcome parameters for proof-of-concept studies with novel anti-neutrophilic drugs are discussed as well as potential safety issues.
Regulated expression of an immunoglobulin kappa gene introduced into a mouse lymphoid cell line. (1982)

We have introduced a functionally rearranged murine kappa light chain immunoglobulin (Ig) gene into an Abelson murine leukemia virus-transformed lymphoid cell line. Plasmid pSV2gpt-kappa 41, containing the kappa light chain gene from the myeloma MOPC41 and the selectable marker gene gpt, was introduced into 81A-2 cells by the calcium phosphate coprecipitation technique. Cells expressing the gpt gene were selected by growth in medium containing mycophenolic acid. One transfected cell line, kappa-2, was shown to make kappa mRNA and polypeptide chains and to assemble the kappa chain product with gamma 2b heavy chains to form an apparently complete IgG2b. When bacterial lipopolysaccharide was added to the growth medium, levels of kappa mRNA and polypeptide increased, showing regulated expression of the introduced kappa gene.
Multiple Protein Analysis of Formalin-fixed and Paraffin-embedded Tissue Samples with Reverse phase Protein Arrays (2013)

Reverse-phase protein arrays (RPPAs) have become an important tool for the sensitive and high-throughput detection of proteins from minute amounts of lysates from cell lines and cryopreserved tissue. The current standard method for tissue preservation in almost all hospitals worldwide is formalin fixation and paraffin embedding, and it would be highly desirable if RPPA could also be applied to formalin-fixed and paraffin embedded (FFPE) tissue. We investigated whether the analysis of FFPE tissue lysates with RPPA would result in biologically meaningful data in two independent studies. In the first study on breast cancer samples, we assessed whether a human epidermal growth factor receptor (HER) 2 score based on immunohistochemistry (IHC) could be reproduced with RPPA. The results showed very good concordance between the IHC and RPPA classifications of HER2 expression. In the second study, we profiled FFPE tumor specimens from patients with adenocarcinoma and squamous cell carcinoma in order to find new markers for differentiating these two subtypes of non-small cell lung cancer. p21-activated kinase 2 could be identified as a new differentiation marker for squamous cell carcinoma. Overall, the results demonstrate the technical feasibility and the merits of RPPA for protein expression profiling in FFPE tissue lysates.
NMR structural studies on antifreeze proteins (1998)

Antifreeze proteins (AFPs) are a structurally diverse class of proteins that bind to ice and inhibit its growth in a noncolligative manner. This adsorption-inhibition mechanism operating at the ice surface results in a lowering of the (nonequilibrium) freezing point below the melting point. A lowering of ~1°C, which is sufficient to prevent fish from freezing in ice-laden seawater, requires millimolar AFP levels in the blood. The solubility of AFPs at these millimolar concentrations and the small size of the AFPs (typically 3-15 kDa) make them ideal subjects for NMR analysis. Although fish AFPs are naturally abundant, seasonal expression, restricted access to polar fishes, and difficulties in separating numerous similar isoforms have made protein expression the method of choice for producing AFPs for structural studies. Expression of recombinant AFPs has also facilitated NMR analysis by permitting isotopic labeling with 15 N and 13 C and has permitted mutations to be made to help with the interpretation of NMR data. NMR analysis has recently solved two AFP structures and provided valuable information about the disposition of ice-binding side chains in a third. The potential exists to solve other AFP structures, including the newly described insect AFPs, and to use solid-state NMR techniques to address fundamental questions about the nature of the interaction between AFPs and ice.Key words: NMR spectroscopy, antifreeze, ice-binding affinity, review.
Low Polydispersity Star Polymers via Cross-Linking Macromonomers by ATRP (2006)

A new method for the synthesis of star polymers with high molecular weight and narrow molecular weight distribution (MWD) is presented. The star copolymers were prepared by atom transfer radical (co)polymerization (ATRP) of linear macromonomers with divinyl cross-linkers using low molar mass initiator. In contrast to prior "arm-first" procedures with macroinitiators, by using lower ratio of concentration of initiator to MM, the star polymers contained less initiating sites in the core, which decreased the extent of star-star coupling reactions and resulted in formation of star polymers with narrower MWD. Addition of more cross-linker and initiator during the reaction increased the star molecular weight and star yield while retaining the narrow MWD of the star polymer. For example, we synthesized a star polymer with molecular weight Mn = 466 000 g/mol and Mw/Mn < 1.2 in >98% yield.
Engineered FGF19 eliminates bile acid toxicity and lipotoxicity leading to resolution of steatohepatitis and fibrosis in mice (2017)

Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well-recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis. Notably, NAFLD patients exhibit a deficiency in fibroblast growth factor 19 (FGF19), an endocrine hormone in the gut-liver axis that controls <i>de novo</i> bile acid synthesis, lipogenesis, and energy homeostasis. Using a mouse model that reproduces the clinical progression of human NAFLD, including the development of simple steatosis, nonalcoholic steatohepatitis (NASH), and advanced "burnt-out" NASH with hepatocellular carcinoma, we demonstrate that FGF19 as well as an engineered nontumorigenic FGF19 analogue, M70, ameliorate bile acid toxicity and lipotoxicity to restore liver health. Mass spectrometry-based lipidomics analysis of livers from mice treated with FGF19 or M70 revealed significant reductions in the levels of toxic lipid species (i.e., diacylglycerols, ceramides and free cholesterol) and an increase in levels of unoxidized cardiolipins, an important component of the inner mitochondrial membrane. Furthermore, treatment with FGF19 or M70 rapidly and profoundly reduced levels of liver enzymes, resolved the histologic features of NASH, and enhanced insulin sensitivity, energy homeostasis, and lipid metabolism. Whereas FGF19 induced hepatocellular carcinoma formation following prolonged exposure in these mice, animals expressing M70 showed no evidence of liver tumorigenesis in this model. <i>Conclusion:</i> We have engineered an FGF19 hormone that is capable of regulating multiple pathways to deliver antisteatotic, anti-inflammatory, and antifibrotic activities and that represents a potentially promising therapeutic for patients with NASH. (<i>Hepatology Communications</i> 2017;1:1024-1042).
Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. (1992)

Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutations were identified by protein-structural analysis followed by allele-specific DNA hybridization to verify the most common types. Slightly retarded (+1) mobility was seen in 80 cases. Of these, 71 had the Arg(-2)----Cys proalbumin variant previously called Malmö I proalbumin. Thirteen examples of the second most frequent type, the substitution Lys313----Asn and a mobility change of -1 charge unit, were found, as well as six cases of Glu570----Lys (albumin B) and a single case of Arg-1----Gln (proalbumin Christchurch). Five previously unreported types of alloalbuminemia were identified: four instances of Glu376----Gln, which is the second known mutation at this site; two examples of Asp550----Ala, the second mutation reported at this site; and one example each of Asp63----Asn, Gln268----Arg, and Asn318----Lys. Other mutations were identified among eight subjects of foreign descent. The high frequency and relatively uniform geographic distribution of the Arg-2----Cys mutation suggest that it may have occurred in a founder individual many generation ago in Sweden.
UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs. Update 2002 (2002)

The 5-and 3-untranslated regions (5-and 3-UTRs) of eukaryotic mRNAs are known to play a crucial role in post-transcriptional regulation of gene expression modulating nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and stability. UTRdb is a specialized database of 5 and 3 untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases including the presence of nucleotide sequence patterns already demonstrated by experimental analysis to have some functional role. All these patterns have been collected in the UTRsite database so that it is possible to search any input sequence for the presence of annotated functional motifs. Furthermore, UTRdb entries have been annotated for the presence of repetitive elements. All Internet resources we implemented for retrieval and functional analysis of 5-and 3-UTRs of eukaryotic mRNAs are accessible at http://bighost.area.ba.cnr.it/ BIG/UTRHome/.
Electric Double-Layer Capacitor Performance of a New Mesoporous Carbon (2000)

A new mesoporous carbon (NMC) was prepared, and its performance in an electric double-layer capacitor (EDLC) was compared to that of a conventional carbon (a molecular-sieving carbon, MSC25). The effect of pore size and pore connection pattern on EDLC performance was demonstrated. To prepare NMC, phenol resin was synthesized inside the pores of an inorganic template, Mobile Composite Material 48 (MCM48), and the resulting resin-template composite was carbonized at 700 degrees C under Ar atmosphere. A coke-like carbonaceous material was obtained after removing the inorganic template by HF treatment. The surface area of NMC was 1257 m(2) g(-1) which is smaller than that of MSC25 (1970 m(2) g(-1)). NMC had three-dimensionally interconnected mesopores (2.3 nm average diam), but randomly connected cage-like micropores (&amp;lt;2.0 nm) were dominant in MSC25. The difference in the pore size and pore connection pattern between the two carbons gave rise to a remarkable difference in their EDLC performances. NMC exhibited a smaller specific capacitance (about 120 F g(-1)) than MSC25 as a result of its smaller surface area, but it showed a higher critical scan rate than the MSC25 electrode due to a smaller resistance-capacitance (RC) time constant. The specific charging capacity of the NMC electrode was about 20 mAh g(-1) and was largely invariant vs. the charge-discharge rate. This was contrasted by MSC25 which showed a steadily decreasing capacity with an increase in rate. As a result, the NMC electrode outperformed the MSC25 based on rate capability. The smaller RC time constant and better rate capability of the NMC electrode apparently arises from the lower electrolyte resistance in pores, which in turn stems from the faster ionic motion in larger pores. (C) 2000 The Electrochemical Society. S0013-4651(00)01-080-6. All rights reserved.
Azomethine Ylides in Organic Synthesis (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Specific Ribosomal DNA Sequences from Diverse Environmental Settings Correlate with Experimental Contaminants (1998)

Phylogenetic analysis of 16S ribosomal DNA (rDNA) clones obtained by PCR from uncultured bacteria inhabiting a wide range of environments has increased our knowledge of bacterial diversity. One possible problem in the assessment of bacterial diversity based on sequence information is that PCR is exquisitely sensitive to contaminating 16S rDNA. This raises the possibility that some putative environmental rRNA sequences in fact correspond to contaminant sequences. To document potential contaminants, we cloned and sequenced PCR-amplified 16S rDNA fragments obtained at low levels in the absence of added template DNA. 16S rDNA sequences closely related to the genera Duganella (formerly Zoogloea), Acinetobacter, Stenotrophomonas, Escherichia, Leptothrix, and Herbaspirillum were identified in contaminant libraries and in clone libraries from diverse, generally low-biomass habitats. The rRNA sequences detected possibly are common contaminants in reagents used to prepare genomic DNA. Consequently, their detection in processed environmental samples may not reflect environmentally relevant organisms.
Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. (1987)

Stimulated human monocytes release several proteins thought to play a role in inflammation, including interleukin 1, tumor necrosis factor, and plasminogen activator. We have purified another proinflammatory protein that is chemotactic for human neutrophils from conditioned medium of lipopolysaccharide-stimulated monocytes. After a series of steps that included anion-exchange chromatography, gel filtration, and HPLC on cation-exchange and reverse-phase columns, an apparently pure protein was obtained that migrated as a single 7-kDa band on NaDodSO4/polyacrylamide gels under reducing or nonreducing conditions. The amino acid composition of this monocyte-derived neutrophil chemotactic factor was different from that of interleukin 1 and tumor necrosis factor. N-terminal amino acid sequence of the first 42 residues was determined. This portion of the molecule has up to 56% sequence similarity with several proteins that may be involved in host responses to infection or tissue injury. It is identical to a portion of a sequence deduced from an mRNA induced by staphylococcal enterotoxin treatment of human leukocytes. At the optimal concentration of 10 nM, 50% of neutrophils added to chemotaxis assay wells migrated toward the pure attractant. Potency and efficacy are comparable to that of fMet-Leu-Phe, which is often used as a reference. In contrast to many attractants, the protein was not chemotactic for human monocytes.
Viscoelastic Effects On A Polyetherimide Cylinder With Constant Radial Deformation (2015)

The relaxation of an axisymmetric radially crimped joint is analyzed with the inner component being formed from the engineering grade polymer ULTEM&lt;sup&gt;TM&lt;/sup&gt; 1000 polyetherimide. Creep and Relaxation tests were performed at several temperatures in order to use Time Temperature Superposition theory to assemble a master curve for predictions at long times based on short time testing.\tThe master curves for each test were fit to the appropriate Prony Series and all coefficients are tabulated for re-use. The elastic theory for the classic thick walled cylinder was reviewed and the conversion from elasticity to viscoelasticity was demonstrated. Strength predictions are shown and compared to their elastic counterparts. Finally, a non-dimensionalized model of strength over time is presented.
Expression and characterization of a recombinant human parathyroid hormone secreted by Escherichia coli employing the staphylococcal protein A promoter and signal sequence. (1990)

Human parathyroid hormone (hPTH) is a peptide hormone consisting of 84 amino acids (hPTH(1-84)). Employing the promoter and signal sequence of Staphylococcus aureus-protein A we have expressed hPTH in Escherichia coli. The expressed proteins are excreted to the growth medium, allowing for rapid and easy purification of the desired products. By amino acid sequence analysis and mass spectrometry, we have shown that the major excreted product is correctly processed human identical hPTH(1-84). The purified recombinant hPTH(1-84) stimulates adenylate cyclase activity in rat osteosarcoma cell membranes to exactly the same extent as synthetic parathyroid hormone standards, indicating that the recombinant product has full biological activity.