gebhart/patrepeval huggingface dataset:
An Efficient Method for the Isolation and Purification of Oligoribonucleotides (1995)

Abstract Problems associated with the use of tetrabutylammonium fluoride like incomplete desilylation and removal of the tetrabutylammonium salts during large scale syntheses of oligoribonucleotides (RNA) have been eliminated by the use of triethylamine trihydrofluoride and precipitation of the RNA with 1-butanol. An efficient anion-exchange HPLC method has been developed for the purification of chemically synthesized RNA and the resulting product precipitated directly by the addition of 1-propanol. A new activator, 5-ethylthio-1H-tetrazole significantly enhances the synthesis quality and yield of oligoribonucleotides. RNA synthesized using these improvements has been shown to be biologically active by a comparative ribozyme-substrate assay.
Activation of recombinant murine cytotoxic cell proteinase-1 requires deletion of an amino-terminal dipeptide. (1993)

Murine cytotoxic cell proteinase-1 (granzyme B) is a member of a family of novel serine proteinases that have been implicated to participate in destruction of target cells by cytotoxic T lymphocytes. Comparison of the sequence of the cDNA with the sequence of the protein isolated from cytoplasmic granules of cytotoxic T lymphocytes suggested that this protein may be synthesized as a preproenzyme containing an amino-terminal activation dipeptide. Here we show that this activation dipeptide regulates the activity of the enzyme in hydrolysis of its preferred substrate tert-butyloxycarbonyl-Ala-Ala-Asp-thiobenzyl ester. Lysates of COS cells transfected with a vector expressing the unmodified cytotoxic cell proteinase-1 cDNA were unable to hydrolyze this substrate, whereas lysates of cells transfected with a construct in which the activation dipeptide codons has been deleted were able to hydrolyze the substrate. In each case Western blotting of the lysates revealed a form of the proteinase with an apparent molecular weight of 27,000. We conclude that the activation dipeptide regulates activity of the enzyme. This is the first report of production of an enzymatically active recombinant cytotoxic T cell serine proteinase. The strategy for successful expression of an activated form of cytotoxic cell proteinase-1 may be applicable to other members of this proteinase family.
A Proposed Taxonomy for the Podocytopathies (2007)

A spectrum of proteinuric glomerular diseases results from podocyte abnormalities. The understanding of these podocytopathies has greatly expanded in recent years, particularly with the discovery of more than a dozen genetic mutations that are associated with loss of podocyte functional integrity. It is apparent that classification of the podocytopathies on the basis of morphology alone is inadequate to capture fully the complexity of these disorders. Herein is proposed a taxonomy for the podocytopathies that classifies along two dimensions: Histopathology, including podocyte phenotype and glomerular morphology (minimal-change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy), and etiology (idiopathic, genetic, and reactive forms). A more complete understanding of the similarities and differences among podocyte diseases will help the renal pathologist and the nephrologist communicate more effectively about the diagnosis; this in turn will help the nephrologist provide more accurate prognostic information and select the optimal therapy for these often problematic diseases. It is proposed that final diagnosis of the podocytopathies should result from close collaboration between renal pathologists and nephrologists and should whenever possible include three elements: Morphologic entity, etiologic form, and specific pathogenic mechanism or association.
Generating production rules from decision trees (1987)

Many inductive knowledge acquisition algorithms generate classifiers in the form of decision trees. This paper describes a technique for transforming such trees to small sets of production rules, a common formalism for expressing knowledge in expert systems. The method makes use of the training set of cases from which the decision tree was generated, first to generalize and assess the reliability of individual rules extracted from the tree, and subsequently to refine the collection of rules as a whole. The final set of production rules is usually both simpler than the decision tree from which it was obtained, and more accurate when classifying unseen cases. Transformation to production rules also provides a way of combining different decision trees for the same classification domain.
1. The synthesis of a cyclopropyl taxane analog via sequential Diels-Alder reactions. 2. The design and synthesis of novel epothilone analogs (1999)

This dissertation describes two independent research projects related to the synthesis of analogs of the microtubule-stabilizing anti-cancer compounds paclitaxel (1) and the epothilones (3 and 4).* The first section describes the application of tandem Diels-Alder methodology to the synthesis, of the cyclopropyl taxane skeleton 79. The construction of 79 is accomplished by an intermolecular Diels-Alder cycloaddition followed by minimal functional group manipulations to prepare for the intramolecular Diels-Alder cycloaddition of 65. The desired trans-B/C ring fusion, as well as the natural C1–C3 hydrogen relationships are established in this cascade. The synthesis of 79 illustrates the power of this methodology for the stereoselective synthesis of complex ring systems from simple acyclic precursors.* The second project described herein illustrates the utility of molecular modeling for the design of novel epothilone analogs. Literature reports highlighting the importance of the eastern hemisphere of epothilone prompted the design of two generations of eastern hemisphere analogs of the molecule, 119 and 167. These analogs were designed with the intention that they would be restricted to adopt the known X-ray conformation in this highly-functionalized region of the molecule.* The key steps in the syntheses of 119 and 167 include diastereoselective aldol reactions and ring-closing olefin metathesis (RCOM) cyclizations. The synthesis of 119 provided the first reported application of RCOM methodology to the synthesis of an eleven-membered ring. The biological evaluation of these analogs allowed us to probe the viability of the eastern hemisphere of the natural product on its own for cytotoxicity. Neither analog proved to be biologically active, however, conformational analysis showed that 167 successfully mimicked the X-ray conformation of the natural product. From these results we concluded that if this is the active conformation for epothilone, the eastern hemisphere alone is not capable of producing the desired biological response.* *Please refer to dissertation for diagrams.
The Phosphorylation State of Eucaryotic Initiation Factor 2 Alters Translational Efficiency of Specific mRNAs (1989)

Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. The importance of eIF-2 alpha phosphorylation in regulating translation was studied by expression of specific mutants of eIF-2 alpha in COS-1 cells. DNA transfection of certain plasmids could activate DAI kinase and result in poor translation of plasmid-derived mRNAs. In these cases, translation of the plasmid-derived mRNAs was improved by the presence of DAI kinase inhibitors or by the presence of a nonphosphorylatable mutant (serine to alanine) of eIF-2 alpha. The improved translation mediated by expression of the nonphosphorylatable eIF-2 alpha mutant was specific to plasmid-derived mRNA and did not affect global mRNA translation. Expression of a serine-to-aspartic acid mutant eIF-2 alpha, created to mimic the phosphorylated serine, inhibited translation of the mRNAs derived from the transfected plasmid. These results substantiate the hypothesis that DAI kinase activation reduces translation initiation through phosphorylation of eIF-2 alpha and reinforce the importance of phosphorylation of eIF-2 alpha as a way to control initiation of translation in intact cells.
A New Class of Continuous Polymer Supports Prepared by Ring-Opening Metathesis Polymerization:  A Straightforward Route to Functionalized Monoliths (2000)

Functionalized monolithic materials have been prepared by ring-opening metathesis copolymerization of norborn-2-ene (NBE) and 1,4,4a,5,8,8a-hexahydro-1,4,5,8-exo,endo-dimethanonaphthalene (DMN-H6) within borosilicate columns in the presence of porogenic solvents such as toluene, methylene chloride, methanol, and 2-propanol. Grubbs-type initiators of the general formula Cl2(PR3)2Ru(CHPh) (R = phenyl, cyclohexyl) were used throughout. The resulting separation media possess microstructures consisting of microporous, spherical microglobules with a narrow microglobule size distribution. By variation of the polymerization conditions in terms of stoichiometry of the monomers, porogenic solvents, and temperature, microglobule diameters may be varied within a range of 2 ± 1 μm up to 30 ± 10 μm. Specific surface areas (σ) and inter-microglobule pore volumes (εz) may be altered within 60−210 m2/g and 2−50%, respectively. Nonfunctionalized separation media were successfully used for the separation of 10 different model proteins using reversed phase chromatography. Generally, high flow rates of up to 10 mL/min indicating fast mass transfer may be applied, resulting in fast and efficient separations. Functionalized continuous rods were synthesized by one additional synthetic step that takes advantage of the living character of the ROMP-based copolymerization. This “in situ” derivatization was achieved after the formation of the continuous rod by reacting the active, surface-bound initiator with functional, norborn-2-ene- and 7-oxanorborn-2-ene-based monomers such as endo,endo-7-oxabicyclo[2.2.1]hept-2-ene-5,6-dicarboxylic anhydride (I), endo/exo-7-oxanorborn-2-ene-5-carboxylic acid (II), endo,endo-N,N-norborn-2-ene-5,6-dicarbimid-l-valine-m-nitroanilide (III), exo,exo-N-phenyl-7-oxabicyclo[2.2.1]hept-2-ene-5,6-dicarbimide (IV), exo,exo-N-(4-(N‘,N‘-dimethylaminophenyl)-7-oxanorborn-2-ene-5,6-dicarbimide (X), endo/exo-norborn-2-ene-5-ylmethylhydroxysiloxyl-β-cyclodextrin (XI), and endo/exo-7-oxanorborn-2-ene-5-carboxyl-β-cyclodextrin (XIII), by passing solutions thereof in dichloromethane and DMF over the rigid rod. A β-cyclodextrin-functionalized continuous rod was successfully used for the enantioselective separation of proglumide (β-blocker).
Rapid Communication : The Synthesis of Mesoporous Materials Using Novel Ionic Liquid Templates in Water (2002)

The alkyltrimethylammonium templates, cited in the original patent for the preparation of MCM-41, have been replaced by a novel set of templates, 1-alkyl-3-methylimidazolium salts. Systematic studies have revealed subtle differences in the performance of the novel templates, and identify them as viable reagents in the synthesis of good quality MCM-41.
In vitro analysis of the homing properties of human lymphocytes: developmental regulation of functional receptors for high endothelial venules (1985)

Circulating lymphocytes leave the blood by binding to specialized high endothelial cells lining postcapillary venules in lymphoid organs or sites of chronic inflammations, migrating through the vessel wall into the surrounding tissue. The capacity of lymphocytes to recognize and bind to high endothelial venules (HEVs) is thus central to the overall process of lymphocyte traffic and recirculation. We show that viable human lymphocytes bind selectively to HEVs in frozen sections of normal human lymph nodes, thus defining a simple in vitro model for the study of human lymphocyte homing properties. Optimal conditions for the quantitative analysis of lymphocyte-HEV interaction are described. Furthermore, by using this assay, we demonstrate that the ability of human lymphocyte populations to bind to HEVs parallels their presumed migratory status in vivo. Thus, thymocytes and bone marrow cells, which are sessile in vivo, bind poorly to HEVs in comparison with mature circulating lymphocytes in peripheral blood or in peripheral lymphoid tissues. These results indicate that HEV-binding ability is a regulated property of mature lymphocytes and, as demonstrated previously in animal models, probably plays a fundamental role in controlling lymphocyte traffic in humans. The in vitro model of lymphocyte-HEV interaction thus provides a unique means to assay the migratory properties of normal and neoplastic human lymphocyte subsets, to analyze the role of lymphocyte traffic mechanisms in normal and pathologic inflammatory reactions, and to define some of the molecular mechanisms responsible for the control of lymphocyte migration and positioning in humans.
A survey of optimization by building and using probabilistic models (2000)

Summarizes the research on population-based probabilistic search algorithms based on modeling promising solutions by estimating their probability distribution and using the constructed model to guide the exploration of the search space. It settles the algorithms in the field of genetic and evolutionary computation where they have been originated. All methods are classified into a few classes according to the complexity of the class of models they use. Algorithms from each of these classes are briefly described and their strengths and weaknesses are discussed.
The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review (2010)

Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leucocytes which infiltrate the colonic mucosa in vast numbers. Myeloid leucocytes such as the CD14(+) CD16(+) monocytes are major sources of tumour necrosis factor (TNF)-α, and therefore selective granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance efficacy of pharmacological therapy. However, studies in IBD have reported both impressive as well as disappointing efficacy outcomes, indicating that patients' demographic factors might determine responders or non-responders to GMA. Nonetheless, this non-drug intervention has an excellent safety profile, and therapeutic GMA is expected to expand. In this review, attempts have been made to compile an update on the mode of actions (MoA) of the Adacolumn GMA. The MoA of GMA appears to be more than adsorption of excess neutrophils and TNF-producing CD14(+) CD16(+) monocytes per se. Adsorbed GMs release interleukin (IL)-1 receptor antagonist, hepatocyte growth factor and soluble TNF receptors, which are anti-inflammatory. Additionally, a sustained increase in lymphocytes including the regulatory CD4(+) CD25(+) T cells (lymphocyte sparing) is seen post-GMA. The impact of GMA on the immune system is potentially very interesting in the context of treating immune-related diseases. Future studies are expected to add intriguing insights to the MoA of GMA.
The science behind dietary omega-3 fatty acids (2008)

Omega-3 fatty acids are being increasingly promoted as important dietary components for health and disease prevention.[1][1],[2][2] These fatty acids are naturally enriched in fatty fish like salmon and tuna and in fish-oil supplements. An increasing number of foods that are not traditional sources
Total Synthesis of (–)‐Epothilone A (1996)

An audacious macroaldolization is the key step in the first total synthesis of the cytotoxic epothilone A, which starts with the units 1, 2, and 3. This condensation closes the ring to form the macrolide, whose structure was determined and published (also in Angewandte Chemie) as recently as July 1996.
The IntAct molecular interaction database in 2010 (2009)

IntAct is an open-source, open data molecular interaction database and toolkit. Data is abstracted from the literature or from direct data depositions by expert curators following a deep annotation model providing a high level of detail. As of September 2009, IntAct contains over 200.000 curated binary interaction evidences. In response to the growing data volume and user requests, IntAct now provides a two-tiered view of the interaction data. The search interface allows the user to iteratively develop complex queries, exploiting the detailed annotation with hierarchical controlled vocabularies. Results are provided at any stage in a simplified, tabular view. Specialized views then allows 'zooming in' on the full annotation of interactions, interactors and their properties. IntAct source code and data are freely available at http://www.ebi.ac.uk/intact.
Fatty Acid Amide Hydrolase, an Enzyme with Many Bioactive Substrates. Possible Therapeutic Implications (2002)

During the last eight years a number of bioactive lipid mediators, the amides or esters of long chain fatty acids, have been discovered or re-discovered. These are: anandamide (N-arachidonoyl-ethanolamine, AEA) and 2-arachidonoylglycerol (2-AG), two endogenous agonists of cannabinoid receptors; oleamide (cis-9-octadecenoamide), a putative endogenous sleep-inducing factor; N-palmitoylethanol amine (PEA), a compound with promising anti-inflammatory and immune-modulatory activity. These compounds are all substrates for the same hydrolytic enzyme, fatty acid amide hydrolase (FAAH), whose molecular characterization was obtained in 1996. The molecular and enzymatic properties, tissue distribution, substrate recognition properties, physiological regulation and biological role of FAAH are discussed in this article, with special emphasis on the possible pharmacological manipulation of the activity of this enzyme with therapeutic purpose.
Analysis of depth of the microporosity in a nickel–chromium system alloy – effects of electrolytic, chemical and sandblasting etching (2003)

The present study was designed to analyse the average depth of the microporosity of a nickel-chromium (Ni-Cr) system alloy (Verabond II). The metal surface was subject to one of the following surface treatment: (i) Electrolytic etching in nitric acid 0.5 N at a current density of 250 mA cm(-2); (ii) chemical etching with CG-Etch etchant; and (iii) Sandblasting with alumina particles 50 microm. Half of the samples were polished before the surface treatments. The depth of porosity was measured through photomicrographs (500x) with a profilometer, and the data were statistically analysed using an analysis of variance (anova) followed by Tukey's test. The conclusions were (i) Differents surface treatment of the Ni-Cr system alloy lead to different depths of microporosity; (ii) The greatest depth of porosity was observed in non-polished alloy; (iii) The greatest and identical depth of microporosity was observed following electrolytic etching and chemical etching; (iv) The least and identical depth of microporosity was observed with chemical etching and sandblasting with alumina particles 50 microm, and (v) Chemical etching showed an intermediary depth.
Efficacy of vaccination on Staphylococcus aureus and coagulase-negative staphylococci intramammary infection dynamics in 2 dairy herds (2014)

The aim of this study was to evaluate vaccine efficacy of a commercial vaccine (Startvac, Hipra Spain) aimed at reducing intramammary infections (IMI) with Staphylococcus aureus and coagulase-negative staphylococci under field conditions. During the 21-mo duration of the study, 1,156 lactations from 809 cows were enrolled in 2 herds. During the first phase of the trial, all cows that were due to calve were vaccinated until approximately 50% of cows in the milking herd were vaccinated (at ~6mo). At that point, when 50% vaccination coverage was reached, cows that were due to calve were randomly assigned to be vaccinated or left as negative controls. Cure rate, rate of new infection, prevalence, and duration of infections were analyzed. Vaccination resulted in a moderate reduction in incidence of new staphylococcal IMI and a more pronounced reduction in duration of IMI associated with reduction of the basic reproduction ratio of Staph. aureus by approximately 45% and of coagulase-negative staphylococci by approximately 35%. The utilization of vaccine in combination with other infection-control procedures, such as excellent milking procedures, treatment, segregation, and culling of known infected cattle, will result in an important reduction in incidence and duration of intramammary staphylococcal infections.
Reducing the peak-to-average power ratio of multicarriermodulation by selected mapping (1996)

The authors propose a method for the reduction of peak-to-average transmit power ratio of multicarrier modulation systems, called selected mapping, is presented, which is appropriate for a wide range of applications. Significant gains can be achieved by selected mapping whereas complexity remains quite moderate.
Guanylyl Cyclase C Messenger RNA Is a Biomarker for Recurrent Stage II Colorectal Cancer (1999)

Expression of guanylyl cyclase C mRNA in lymph nodes is associated with recurrence of colorectal cancer in patients with stage II disease. Analysis of guanylyl cyclase mRNA expression by RT-PCR may be useful for colorectal cancer staging.
The impact of strain diversity and mixed infections on the evolution of resistance to Bacillus thuringiensis (2013)

Pesticide mixtures can reduce the rate at which insects evolve pesticide resistance. However, with live biopesticides such as the naturally abundant pathogen Bacillus thuringiensis (Bt), a range of additional biological considerations might affect the evolution of resistance. These can include ecological interactions in mixed infections, the different rates of transmission post-application and the impact of the native biodiversity on the frequency of mixed infections. Using multi-generation selection experiments, we tested how applications of single and mixed strains of Bt from diverse sources (natural isolates and biopesticides) affected the evolution of resistance in the diamondback moth, Plutella xylostella, to a focal strain. There was no significant difference in the rate of evolution of resistance between single and mixed-strain applications although the latter did result in lower insect populations. The relative survivorship of Bt-resistant genotypes was higher in the mixed-strain treatment, in part owing to elevated mortality of susceptible larvae in mixtures. Resistance evolved more quickly with treatments that contained natural isolates, and biological differences in transmission rate may have contributed to this. Our data indicate that the use of mixtures can have unexpected consequences on the fitness of resistant and susceptible insects.
Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers (2005)

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA-peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 x 10(3)/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.