gebhart/patrepeval huggingface dataset:
Poly(dimethylsiloxane)/poly(hexamethylene oxide) mixed macrodiol based polyurethane elastomers. I. Synthesis and properties (2000)

The compatibilizing effect of poly(hexamethylene oxide) (PHMO) on the synthesis of polyurethanes based on α,ω-bis(6-hydroxyethoxypropyl) poly(dimethylsiloxane) (PDMS) was investigated. The hard segments of the polyurethanes were based on 4,4′-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol. The effects of the PDMS/PHMO composition, method of polyurethane synthesis, hard segment weight percentage, catalyst, and molecular weight of the PDMS on polyurethane synthesis, properties, and morphology were investigated using size exclusion chromatography, tensile testing, and differential scanning calorimetry (DSC). The large difference in the solubility parameters between PDMS and conventional reagents used in polyurethane synthesis was found to be the main problem associated with preparing PDMS-based polyurethanes with good mechanical properties. Incorporation of a polyether macrodiol such as PHMO improved the compatibility and yielded polyurethanes with significantly improved mechanical properties and processability. The optimum PDMS/PHMO composition was 80 : 20 (w/w), which yielded a polyurethane with properties comparable to those of the commercial material Pellethane™ 2363-80A. The one-step polymerization was sensitive to the hard segment weight percentage of the polyurethane and was limited to materials with about a 40 wt % hard segment; higher concentrations yielded materials with poor mechanical properties. A catalyst was essential for the one-step process and tetracoordinated tin catalysts (e.g., dibutyltin dilaurate) were the most effective. Two-step bulk polymerization overcame most of the problems associated with reactant immiscibility by the end capping of the macrodiol and required no catalysts. The DSC results demonstrated that in cases where poor properties were observed, the corresponding polyurethanes were highly phase separated and the hard segments formed were generally longer than the average expected length based on the reactant stoichiometry. Based on these results, we postulated that at low levels (∼ 20 wt %) the soft segment component derived from PHMO macrodiol was concentrated mainly in the interfacial regions, strengthening the adhesion between hard and soft domains of PDMS-based polyurethanes. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 2026–2040, 2000
Rapid tests for sexually transmitted infections (STIs): the way forward (2006)

In the developing world, laboratory services for sexually transmitted infections (STIs) are either not available, or where limited services are available, patients may not be able to pay for or physically access those services. Despite the existence of national policy for antenatal screening to prevent congenital syphilis and substantial evidence that antenatal screening is cost-effective, implementation of syphilis screening programmes remains unacceptably low because of lack of screening tools that can be used in primary health care settings. The World Health Organization Sexually Transmitted Diseases Diagnostics Initiative (SDI) has developed the ASSURED criteria as a benchmark to decide if tests address disease control needs: Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end-users. Rapid syphilis tests that can be used with whole blood approach the ASSURED criteria and can now be deployed in areas where no previous screening has been possible. Although rapid tests for chlamydia and gonorrhoea lack sensitivity, more tests are in development. The way forward for STI diagnostics requires a continuing quest for ASSURED tests, the development of a road map for test introduction, sustainable programmes for quality assurance, and the creation of a robust infrastructure linked to HIV prevention that ensures sustainability of STI control efforts that includes viral STIs.
The nucleotide sequence of thetnpAgene of Tn21 (1987)

The nucleotide sequence of the tnpA gene of Tn21 is presented. The transposase encoded by this gene is exactly the same length (988 amino acids) as the Tn501 transposase (4), and shows 72% homology overall with this protein, with greater homology towards the C-terminus. The sequence of the transposase is discussed in the context of the evolution of Class II transposable elements and of the characteristics of the enzyme's action.
A Convenient Method for the Conversion of α-Tetralones to Aryl Acetates (1991)

Abstract A facile synthesis of aryl acetates from α-tetralone has been performed with isopropenyl acetate and p-toluenesulfonic acid, followed by dehydrogenation with air or DDQ, in a one-pot procedure.
Porphyrin Light‐Harvesting Arrays Constructed in the Recombinant Tobacco Mosaic Virus Scaffold (2007)

We have demonstrated the construction of multiple porphyrin arrays in the tobacco mosaic virus (TMV) supramolecular structures by self-assembly of recombinant TMV coat protein (TMVCP) monomers, in which Zn-coordinated porphyrin (ZnP) and free-base porphyrin (FbP) were site-selectively incorporated. The photophysical properties of porphyrin moieties incorporated in the TMV assemblies were also characterized. TMV-porphyrin conjugates employed as building blocks self-assembled into unique disk and rod structures under the proper conditions as similar to native TMV assemblies. The mixture of a ZnP donor and an FbP acceptor was packed in the TMV assembly and showed energy transfer and light-harvesting activity. The detailed photophysical properties of the arrayed porphyrins in the TMV assemblies were examined by time-resolved fluorescence spectroscopy, and the energy transfer rates were determined to be 3.1-6.4x10(9) s(-1). The results indicate that the porphyrins are placed at the expected positions in the TMV assemblies.
Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies (2016)

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.
Neutralization of HIV-1 by redirection of natural antibodies (2008)

The great variability and high glycosylation of gp120 poses a great challenge for the design of a functional immune therapy. The binding region of the CD4 receptor to gp120, however, is well conserved and may constitute a target to limit viral entry and infectivity. Our strategy consists in using a preexisting pool of natural antibodies directed toward the gal(alpha1,3)gal disaccharide and to redirect it to HIV. We here show that using CD4-derived, gp120-binding, synthetic peptides chemically linked to gal(alpha1,3)gal can redirect these natural antibodies and improve the HIV-1 neutralizing activity of the CD4-derived peptides in vitro. Importantly, the binding of the CD4-gal(alpha1,3)gal peptides to HIV-1-infected cells conferred antibody-dependent cellular cytotoxicity after the addition of human sera. Thus, the temporary redirection of naturally occurring antibodies and their biological activities to a new antigen represents a completely new way of targeting a human disease.
Inhibition (1992)

In everyday parlance, "inhibition" suggests repression, tight control, the opposite of freedom. In medicine and psychotherapy the term is commonplace, its definition understood. Relating how inhibition--the word and the concept--became a bridge between society at large and the natural sciences of mind and brain, Smith constructs an engagingly original history of our view of ourselves. Not until the late nineteenth century did the term "inhibition" become common in English, connoting the dependency of reason and of civilization itself on the repression of "the beast within." This usage followed a century of Enlightenment thought about human nature and the nature of the human mind. Smith traces theories of inhibitory control from the moralistic psychologies of the early nineteenth century to the famous twentieth-century schools of Sherrington, Pavlov, and Freud. He finds that the meanings of "inhibition" cross disciplinary boundaries and outline the growth of our belief in the self-regulated person.
Engineering a Bacillus subtilis expression-secretion system with a strain deficient in six extracellular proteases (1991)

We describe the development of an expression-secretion system in Bacillus subtilis to improve the quality and quantity of the secreted foreign proteins. This system consists of a strain (WB600) deficient in six extracellular proteases and a set of sacB-based expression vectors. With the inactivation of all six chromosomal genes encoding neutral protease A, subtilisin, extracellular protease, metalloprotease, bacillopeptidase F, and neutral protease B, WB600 showed only 0.32% of the wild-type extracellular protease activity. No residual protease activity could be detected when WB600 was cultured in the presence of 2 mM phenylmethylsulfonyl fluoride. By using TEM beta-lactamase as a model, we showed that WB600 can significantly improve the stability of the secreted enzyme. To further increase the production level we constructed an expression cassette carrying sacY, a sacB-specific regulatory gene. This gene was placed under the control of a strong, constitutively expressed promoter, P43. With this cassette in the expression vector, an 18-fold enhancement in beta-lactamase production was observed. An artificial operon, P43-sacY-degQ, was also constructed. However, only a partial additive enhancement effect (24-fold enhancement) was observed. Although degQ can stimulate the production of beta-lactamase in the system, its ability to increase the residual extracellular protease activity from WB600 limits its application. The use of the P43-sacY cassette and WB600 would be a better combination for producing intact foreign proteins in high yield.
Growth Hormone Stimulates Proliferation of Old–Aged Regenerating Liver Through Forkhead Box M1b (2003)

The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and the members of which play essential roles in cellular proliferation, differentiation, and longevity. Reduced cellular proliferation during aging is associated with a progressive decline in both growth hormone (GH) secretion and Foxm1b expression. Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated that increased hepatocyte expression of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver. GH therapy in older people has been shown to cause an increase in cellular proliferation, but the transcription factors that mediated this stimulation in proliferation remain uncharacterized. In this study, we showed that human GH administration to old-aged Balb/c mice dramatically increased both expression of Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged regenerating hepatocyte proliferation was associated with elevated protein expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of cyclin-dependent kinase inhibitor p27(Kip1) (p27). GH treatment also was found to stimulate hepatocyte proliferation and expression of Foxm1b protein without partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b -/- mice failed to restore regenerating hepatocyte DNA replication and mitosis caused by Foxm1b deficiency. These genetic studies provided strong evidence that the presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte proliferation. In conclusion, our old-aged liver regeneration studies show that increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation, thus providing a mechanism for GH action in the elderly.
Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents (2009)

For the past 15-20 years, the intracellular delivery and silencing activity of oligodeoxynucleotides have been essentially completely dependent on the use of a delivery technology (e.g. lipofection). We have developed a method (called 'gymnosis') that does not require the use of any transfection reagent or any additives to serum whatsoever, but rather takes advantage of the normal growth properties of cells in tissue culture in order to promote productive oligonucleotide uptake. This robust method permits the sequence-specific silencing of multiple targets in a large number of cell types in tissue culture, both at the protein and mRNA level, at concentrations in the low micromolar range. Optimum results were obtained with locked nucleic acid (LNA) phosphorothioate gap-mers. By appropriate manipulation of oligonucleotide dosing, this silencing can be continuously maintained with little or no toxicity for >240 days. High levels of oligonucleotide in the cell nucleus are not a requirement for gene silencing, contrary to long accepted dogma. In addition, gymnotic delivery can efficiently deliver oligonucleotides to suspension cells that are known to be very difficult to transfect. Finally, the pattern of gene silencing of in vitro gymnotically delivered oligonucleotides correlates particularly well with in vivo silencing. The establishment of this link is of particular significance to those in the academic research and drug discovery and development communities.
Substance‐P receptors in human primary neoplasms: Tumoral and vascular localization (1995)

Primary human neoplasms were examined for the presence of substance-P receptors by receptor autoradiography with 125I-labelled Bolton-Hunter substance P. Substance-P receptors were localized and characterized in the neoplastic cells of 9/12 astrocytomas, 10/10 glioblastomas, 10/12 medullary thyroid carcinomas, 8/16 breast carcinomas and 4/5 ganglioneuroblastomas. Conversely, substance-P receptors were not or only rarely identified on non-small-cell carcinomas of the lung (1/16), neuroblastomas (0/8), adenocarcinomas of the colon (1/21) or the pancreas (1/9), or on malignant lymphomas (3/18). However, in the great majority of the investigated tumours, substance-P receptors were found on intra- and peritumoral blood vessels. All substance-P receptors detected had the pharmacological characteristics of the neurokinin-I receptor sub-type. In addition, the expression of somatostatin receptors was examined in all the neoplastic tissues mentioned above. Both substance-P and somatostatin receptors were present in astrocytomas and in ganglioneuroblastomas, whereas little or no receptor was found in pancreatic and non-small-cell lung carcinomas. The extent of somatostatin-receptor expression was inversely correlated to that of the substance-P receptors in glioblastomas, neuroblastomas and non-Hodgkin's lymphomas. The tumoral and vascular localization of substance-P receptors in tumours may have clinical implications. The use of radiolabelled substance P for in vivo scintigraphy may supplement the current set of diagnostic tools. Substance-P antagonists might be used in the treatment of tumours, as their binding to vascular receptors may decrease tumoral blood supply and drainage.
The alpha v beta 5 integrin receptor regulates receptor-mediated endocytosis of vitronectin (1993)

Vitronectin is an adhesive glycoprotein that binds to the extracellular matrix and interacts with integrin receptors on the surface of adherent cells. Previous studies have demonstrated that the conformationally altered, heparin binding form of vitronectin is removed from the matrix by receptor-mediated endocytosis and degraded through a lysosomal pathway (Panetti, T. S., and McKeown-Longo, P. J. (1993) J. Biol. Chem. 268, 11988-11993). The present studies were undertaken to determine the role of cell surface integrins in the endocytosis and degradation of vitronectin. RGDS peptides, used to disrupt the binding of vitronectin to cell surface integrins, inhibited degradation of vitronectin but had no effect on the binding of vitronectin to the cell layer. Localization of vitronectin in the cell layer by indirect immunofluorescence indicated that the RGDS peptides inhibited degradation by preventing the internalization of vitronectin by the cells. To determine which vitronectin receptor was involved in mediating the endocytosis, vitronectin degradation was measured in the presence of monoclonal antibodies. Antibodies against the alpha v beta 5 but not the alpha v beta 3 integrin inhibited degradation of vitronectin by 80%. This study demonstrates a new role for integrins in regulating internalization and degradation of molecules from the extracellular matrix.
Rotation of Molecular Hydrogen in Si: Unambiguous Identification of Ortho-H2and Para-D2 (2002)

The 3618.4 and $2642.6{\mathrm{cm}}^{\ensuremath{-}1}$ infrared absorption lines of interstitial ${\mathrm{H}}_{2}$ and ${\mathrm{D}}_{2}$ in silicon have been studied under applied uniaxial stresses. The resulting splittings and their small dependence on isotope establish that ${\mathrm{H}}_{2}$ in Si is a nearly free rotor and that these lines arise from vibrational transitions between rovibrational states with rotational quantum number $J\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1$ ( ${T}_{2}$ in ${T}_{d}$ symmetry) for ortho- ${\mathrm{H}}_{2}$ and para- ${\mathrm{D}}_{2}$.
Peptides : chemistry and biology : proceedings of the tenth American Peptide Symposium, May 23-28, 1987, St. Louis, Missouri, U.S.A. (1988)

The Tenth American Peptide Symposium was held on the campus of Wash ington University in St. Louis, Missouri, on May 23-28, 1987. More than 750 participants from around the world met to renew acquaintances, make new friends, and feast at the scientific explosion occurring in the field of peptide research. From over 85 oral presentations and 295 poster presentations, the manuscripts which make up this proceedings have been selected in order to present a synopsis of current research. In many ways, this meeting represented a culmination of forces clearly perceptible in the proceedings of previous meetings in which synthetic chemistry, spectroscopy, molecular biology, molecular modeling, and protein chemistry all are blended as needed to focus on interesting scientific problems. As peptides assume an ever increasingly important role in biological phenomena, our domain as peptide chemists has obviously expanded, and we are the richer for it. The session on conformation was highlighted by both predictions ofthree-dimensional structures of proteins (i. e., interleukin and human growth hormone) as well as determination of solution structures by 2D NMR. A growing interest in peptide mimetics stimulated much interest in reverse turn mimics, nonpeptide antagonists of peptide hormones, and amide bond isosteres. Increased use of unusual amino acids created strong interest in approaches to asymmetric syntheses of amino acids and methodological improvements in peptide synthesis as well as recent advances in purification and characterization methods.
What is the Jeopardy Model? A Quasi-Synchronous Grammar for QA (2007)

This paper presents a syntax-driven approach to question answering, specifically the answer-sentence selection problem for short-answer questions. Rather than using syntactic features to augment existing statistical classifiers (as in previous work), we build on the idea that questions and their (correct) answers relate to each other via loose but predictable syntactic transformations. We propose a probabilistic quasi-synchronous grammar, inspired by one proposed for machine translation (D. Smith and Eisner, 2006), and parameterized by mixtures of a robust nonlexical syntax/alignment model with a(n optional) lexical-semantics-driven log-linear model. Our model learns soft alignments as a hidden variable in discriminative training. Experimental results using the TREC dataset are shown to significantly outperform strong state-of-the-art baselines. 1
The amino acid sequence of yeast enolase. (1981)

Automatic sequencing of yeast enolase and of its chemically and enzymatically produced peptide fragments has established the sequence of 416 of the 436 residues in the enolase subunits. The missing segments have been provided from results from sequencing the DNA of the yeast enolase genes (Holland, M. J., Holland, J. P., Thill, G. P., and Jackson, K. A. (1981) J. Biol. Chem. 256, 1385-1395). The reported enolase sequence thus represents the results of two completely independent studies, which yielded identical results for 404 of the 436 residues, and which on re-examination are consistent with the reported sequence in all but nine positions. The availability of the entire yeast enolase sequence has permitted a reassessment of structure-function parameters available for the enzyme, and some implications of the sequence information on the secondary, tertiary, and quarternary structure and on the active site components of yeast enolase have been summarized and discussed.
The fundamentals of bubble evolution (1995)

S. D. Lubetkin, Chem. Soc. Rev., 1995, 24, 243 DOI: 10.1039/CS9952400243
Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes. (1999)

Sodium salicylate (NaSal) and other nonsteroidal anti-inflammatory drugs (NSAIDs) coordinately inhibit the activity of NF-kappa B, activate heat shock transcription factor 1 and suppress cytokine gene expression in activated monocytes and macrophages. Because our preliminary studies indicated that these effects could be mimicked by inhibitors of signal transduction, we have studied the effects of NSAIDs on signaling molecules potentially downstream of LPS receptors in activated macrophages. Our findings indicate that ribosomal S6 kinase 2 (RSK2), a 90-kDa ribosomal S6 kinase with a critical role as an effector of the RAS-mitogen-activated protein kinase pathway and a regulator of immediate early gene transcription is a target for inhibition by the NSAIDs. NSAIDs inhibited the activity of purified RSK2 kinase in vitro and of RSK2 in mammalian cells and suppressed the phosphorylation of RSK2 substrates cAMP response element binding protein (CREB) and I-kappa B alpha in vivo. Additionally, NaSal inhibited the phosphorylation by RSK2 of CREB and I-kappa B alpha on residues crucial for their transcriptional activity in vivo and thus repressed CREB and NF-kappa B-dependent transcription. These experiments suggest that RSK2 is a target for NSAIDs in the inhibition of monocyte-specific gene expression and indicate the importance of RSK2 and related kinases in cell regulation, indicating a new area for anti-inflammatory drug discovery.