gebhart/patrepeval huggingface dataset:
Mapping of the RNA-binding and endoribonuclease domains of NIPP1, a nuclear targeting subunit of protein phosphatase 1 (1999)

NIPP1 (351 residues) is a major regulatory and RNA-anchoring subunit of protein phosphatase 1 in the nucleus. Using recombinant and synthetic fragments of NIPP1, the RNA-binding domain was mapped to the C-terminal residues 330-351. A synthetic peptide encompassing this sequence equalled intact NIPP1 in RNA-binding affinity and could be used to dissociate NIPP1 from the nuclear particulate fraction. An NIPP1 fragment consisting of residues 225-351 (Ard1/NIPP1gamma), that may be encoded by an alternatively spliced transcript in transformed B-lymphocytes, displayed a single-strand Mg(2+)-dependent endoribonuclease activity. However, full-length NIPP1 and NIPP1(143-351) were not able to cleave RNA, indicating that the endoribonuclease activity of NIPP1 is restrained by its central domain. The endoribonuclease activity was also recovered in the RNA-binding domain, NIPP1(330-351), but with a 30-fold lower specific activity. Thus, the endoribonuclease catalytic site and the RNA-binding site both reside in the C-terminal 22 residues of NIPP1. The latter domain does not conform to any known nucleic-acid binding motif.
Toward the development of new medicinal leads with selectivity for protein kinase C isozymes (2005)

Tumor promoters such as phorbol esters bind strongly to protein kinase C (PKC) isozymes to induce their activation. Since each PKC isozyme is involved in diverse biological events in addition to tumor promotion, the isozymes serve as promising therapeutic targets. Tumor promoters bind to the C1A and/or C1B domain of conventional (alpha, betaI, betaII, and gamma) and novel PKC isozymes (delta, epsilon, eta, and theta). As these C1 domains play differential roles in PKC activation and their translocation in cells, the development of agents with binding selectivity for individual C1 domains is a pressing need. For this purpose, we established a synthetic C1 peptide library of all PKC isozymes. The library enabled us to identify indolactam-V (1) as a promising lead compound. Our diverse structure-activity studies on 1 indicated that the position of the hydrophobic substituent on the indole ring dominates the PKC isozyme- and C1 domain-selective binding rather than conformation of the nine-membered lactam. Moreover, we suggested that the indole ring of 1 could be involved in the CH/pi interaction with Pro-11 of the C1B domain of PKCdelta. This invaluable information will lead to the structural optimization of the PKCdelta ligand as exemplified by the design and synthesis of naphtholactam-V8 (21).
Structure of flexible and semiflexible polyelectrolyte chains in confined spaces of slit micro/nanochannels (2007)

Understanding the behavior of a polyelectrolyte in confined spaces has direct relevance in design and manipulation of microfluidic devices, as well as transport in living organisms. In this paper, a coarse-grained model of anionic semiflexible polyelectrolyte is applied, and its structure and dynamics are fully examined with Brownian dynamics (BD) simulations both in bulk solution and under confinement between two negatively charged parallel plates. The modeling is based on the nonlinear bead-spring discretization of a continuous chain with additional long-range electrostatic, Lennard-Jones, and hydrodynamic interactions between pairs of beads. The authors also consider the steric and electrostatic interactions between the bead and the confining wall. Relevant model parameters are determined from experimental rheology data on the anionic polysaccharide xanthan reported previously. For comparison, both flexible and semiflexible models are developed accompanying zero and finite intrinsic persistence lengths, respectively. The conformational changes of the polyelectrolyte chain induced by confinements and their dependence on the screening effect of the electrolyte solution are faithfully characterized with BD simulations. Depending on the intrinsic rigidity and the medium ionic strength, the polyelectrolyte can be classified as flexible, semiflexible, or rigid. Confined flexible and semiflexible chains exhibit a nonmonotonic variation in size, as measured by the radius of gyration and end-to-end distance, with changing slit width. For the semiflexible chain, this is coupled to the variations in long-range bond vector correlation. The rigid chain, realized at low ionic strength, does not have minima in size but exhibits a sigmoidal transition. The size of confined semiflexible and rigid polyelectrolytes can be well described by the wormlike chain model once the electrostatic effects are taken into account by the persistence length measured at long length scale.
100 Years of Baeyer–Villiger Oxidations (1999)

In the present review, we report the discovery of the formation of esters and lactones by oxidation of ketones with a peroxide derivative, namely the Baeyer–Villiger reaction. This reaction was first reported by Adolf von Baeyer and Victor Villiger a century ago in 1899, just one year after the oxidant they used (KHSO5) has been described. Furthermore, Baeyer and Villiger established the composition of this new inorganic peroxide and showed that its instability was the reason of a controversy between several European chemists between 1878 and 1893. For the first 50 years the mechanism of the Baeyer–Villiger reaction was a matter of debate. A side product, 1,2,4,5-tetraoxocyclohexane, was ruled out as an intermediate in the ester formation by Dilthey. Criegee postulated a nucleophilic attack of the oxidant on the carbonyl group. This mechanism was confirmed by von E. Doering by a labeling experiment with [18O]benzophenone. The rearrangement step occurs with retention of the stereochemistry at the migrating center. The competitive migration and the rate-determining step are also discussed in this review.
Enhancement of Transdermal Drug Delivery: Chemical and Physical Approaches (2000)

Transdermal drug delivery has been intensively studied over the last two decades because of the many advantages offered by this route of administration. However, the number of drugs used in transdermal drug delivery systems has been somewhat limited, in part resulting from the formidable barrier to drug permeation presented by the upper layer of the skin, the stratum corneum. In order to overcome this, different strategies have been implemented to render the skin more permeable to drugs. These strategies include both chemical and physical approaches. In this review, we outline the enhancing activities and mechanisms of action of some of the more extensively studied chemical penetration enhancers (oxazolidinones, propylene glycol, and epidermal enzymes). In addition, we discuss novel physical strategies, such as the use of microneedles or electroporation.
PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE (1993)

Proteins that transit the constitutive pathway of secretion frequently require proteolytic processing after a pair of basic amino acids to attain their full functional activity. A ubiquitously expressed calcium-dependent subtilisin-like serine protease, named PACE or furin, can cleave precursor polypeptides specifically at pairs of basic amino acids where an arginine residue is present in the P4 position. Another member of this protease family, PACE4, was cloned recently by a PCR-based strategy and was also shown to be ubiquitously expressed. We have expressed PACE4 by transient DNA transfection of COS-1 cells and have shown that the cDNA encodes a 120-kDa polypeptide that is present in cell extracts but not in conditioned medium of transfected cells. The substrate specificities of PACE and PACE4 for cleavage of pro-von Willebrand factor were studied in parallel using a transient DNA cotransfection system. Like PACE, PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine. These data, taken together with previously published data showing that PACE4 cannot process pro-factor IX, demonstrate that PACE and PACE4 have overlapping but not identical substrate specificities. Further differences between PACE and PACE4 specificities were elucidated by monitoring inhibition of processing activity mediated by the serine protease inhibitor alpha 1-antitrypsin Pittsburgh mutant. Pro-vWF processing by PACE was inhibited by expression of the alpha 1-antitrypsin Pittsburgh mutant, whereas processing of pro-vWF by PACE4 was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct‐Write Assembly of 3D Hydrogel Scaffolds for Guided Cell Growth (2009)

Planar and 3D hydrogel scaffolds are patterned via direct-write assembly of hydrogel-based inks. Through simultaneous ink writing and UV polymerization, both 1D and 3D microperiodic scaffolds are created. 3T3 murine fibroblasts are seeded onto the scaffolds and their process development is observed using fluorescence microscopy.
Quality of Life in OCD: Differential Impact of Obsessions, Compulsions, and Depression Comorbidity (2003)

Given the importance of these symptoms, treatments that directly target obsessions and secondary depression symptoms in OCD are warranted. However, replication of these findings in a prospective cohort study is required, because although the the current study's cross-sectional design allows for the examination of the associations among obsessions, depression, and QOL, it cannot establish their temporal framework (that is, causal relations).
A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function (2001)

The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has remained unclear. To address this issue, we generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of these mice had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction of hypoxia-responsive genes involved in energy metabolism, and an abnormal response to beta-adrenergic stimulation. These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function. Further, they establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.
Differential Roles of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Angiogenesis (2006)

Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis, binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). These receptors regulate physiological as well as pathological angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the major signals for angiogenesis. However, unlike other representative tyrosine kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase-Cgamma-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2 is a direct signal transducer for pathological angiogenesis including cancer and diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical targets for the suppression of these diseases. VEGFR1 plays dual role, a negative role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not only in endothelial cells but also in macrophage-lineage cells, and promotes tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1 was found to be present at abnormally high levels in the serum of preeclampsia patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is also an important target in the treatment of human diseases. Recently, the VEGFR2-specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly, the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic response in mice with minor side effects such as inflammation compared with VEGF-A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.
Raman spectroscopy (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRaman spectroscopyD. L. GerrardD. L. GerrardMore by D. L. Gerrard and J. BirnieJ. BirnieMore by J. BirnieCite this: Anal. Chem. 1990, 62, 12, 140–150Publication Date (Print):June 15, 1990Publication History Published online1 May 2002Published inissue 15 June 1990https://pubs.acs.org/doi/10.1021/ac00211a012https://doi.org/10.1021/ac00211a012research-articleACS PublicationsRequest reuse permissionsArticle Views947Altmetric-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
Reprogramming of 3′ Untranslated Regions of mRNAs by Alternative Polyadenylation in Generation of Pluripotent Stem Cells from Different Cell Types (2009)

Taken together, these findings indicate that reprogramming of 3'UTRs by APA, which result from regulation of both general polyadenylation activity and cell type-specific factors and can reset post-transcriptional gene regulatory programs in the cell, is an integral part of iPS cell generation, and the APA pattern can be a good biomarker for cell type and state, useful for sample classification. The results also suggest that perturbation of the mRNA polyadenylation machinery or RNA processing activity may facilitate generation of iPS cells.
Noncatalytic Interactions between Glutathione S-Transferases and Nitroalkene Fatty Acids Modulate Nitroalkene-Mediated Activation of Peroxisomal Proliferator-Activated Receptor γ (2009)

The naturally occurring nitroalkenes, nitrolinoleic (NO(2)-LA) and nitrooleic (NO(2)-OA) acids, are among the most potent endogenous ligand activators of PPARgamma-dependent transcription. In order to understand mechanisms that regulate cellular response to these nitroalkenes, we previously demonstrated that glutathione conjugation of NO(2)-LA and MRP1-mediated efflux of the conjugates were associated with significant attenuation of PPARgamma activation by this nitroalkene [(2006) Biochemistry 45, 7889-7896]. Here we show that NO(2)-OA activation of PPARgamma is similarly affected by nonenzymatic conjugation and MRP1-mediated efflux. Moreover, the roles of glutathione S-transferases (GSTs) in the glutathione conjugation and bioactivities of NO(2)-LA and NO(2)-OA were investigated. While none of the GST isozymes tested (GSTA1-1, A4-4, M1a-1a, and P1a-1a) enhanced the rate of glutathione conjugation, expression of GSTA1-1, M1a-1a, or P1a-1a in MCF7 cells significantly reduced the magnitude of PPARgamma-dependent reporter gene transcription in response to NO(2)-LA and NO(2)-OA treatment, with GSTP1a-1a expression mediating the most potent inhibition of PPARgamma. Although these GSTs failed to catalyze nitroalkene conjugation with glutathione, the nitroalkenes were found to associate avidly with all four GST isozymes as indicated by their ability to inhibit GST activity with K(i)'s in the nanomolar range. Treatment of purified GSTP1a-1a with excess NO(2)-LA and NO(2)-OA resulted in the formation of covalent adducts between GSTP1a monomers and nitroalkenes, although separate experiments indicated that such covalent bond formation was not necessary for avid GST-nitroalkene interactions. These results suggest that GSTs can inhibit the activation of transcription by nitroalkenes via noncatalytic sequestration of these ligands, and their glutathione conjugates, away from their nuclear target, PPARgamma.
Mucoadhesion and the Gastrointestinal Tract (2008)

The concept of mucoadhesion is one that has the potential to improve the highly variable residence times experienced by drugs and dosage forms at various sites in the gastrointestinal tract, and consequently, to reduce variability and improve efficacy. Intimate contact with the mucosa should enhance absorption or improve topical therapy. A variety of approaches have been investigated for mucoadhesion in the gastrointestinal tract, particularly for the stomach and small intestine. Despite interesting results in these sites, mucoadhesive approaches have not yet shown success in humans. The potential of the lower gut for these applications has been largely neglected, although the large intestine in particular may benefit, and the colon has several factors that suggest mucoadhesion could be successful there, including lower motility and the possibility of a lower mucus turnover and thicker mucus layer. In vitro studies on colonic mucoadhesion show promise, and rectal administration has shown some positive results in vivo. This review considers the background to mucoadhesion with respect to the physiological conditions of the gastrointestinal tract as well as the principles that underlie this concept. Mucoadhesive approaches to gastrointestinal drug delivery will be examined, with particular attention given to the lower gut.
KScript and KSWorld (2013)

We report on a language called KScript and a GUI framework called KSWorld. The goal of KScript and KSWorld is to try to reduce the accidental complexity in GUI framework code and application building. We aim for an understandable, concise way to specify an application's behavior and appearance, minimizing extra details that arise only because of the medium being used.
Streptococcal cell wall-induced arthritis. Requirements for neutrophils, P-selectin, intercellular adhesion molecule-1, and macrophage-inflammatory protein-2 (1997)

Immune arthritis in rat ankle joints was induced by intra-articular injection of streptococcal cell was extract (SCW), followed 21 days later by i.v. injection of SCW. This results in a monoarticular arthritis characterized by an influx of neutrophils and mononuclear cells, a 35-fold increase in urinary excretion of 8-hydroxy-deoxyguanosine (8-OH-dGUA; an index of free radical production), ankle edema, and joint damage/destruction. Neutrophil depletion substantially reduced the intensity of ankle edema. Ab-induced blockade of P-selectin or ICAM-1 also reduced the intensity of ankle edema and the influx of neutrophils. Blockade of TNF-alpha or IL-1 resulted in nearly complete and persistent reduction in ankle edema and profound reductions in the accumulation of neutrophils and mononuclear cells in affected joints. Finally, blocking of macrophage-inflammatory protein-2 reduced ankle edema and neutrophil accumulation during the first 2 days after i.v. challenge with SCW. These data indicate that SCW-induced arthritis is neutrophil dependent and that the recruitment of neutrophils and subsequent joint edema requires ICAM-1, P-selectin, and macrophage-inflammatory protein-2, as well as TNF-alpha and IL-1.
Signaling Actions of Electrophiles: Anti-inflammatory Therapeutic Candidates (2010)

Over the past several years, research on biologically relevant electrophiles has been replete with new insights, expanding our understanding of the roles electrophiles play in vivo. Importantly, many electrophiles can form reversible covalent adducts with both proteins and small-molecule thiols in cells. This post-translational protein modification has important ramifications, including changes in protein enzymatic activity, the transduction of signals within and between cells, and alterations in gene expression. Electrophiles modulate a variety of cellular signaling processes that are involved in several major diseases with inflammatory components. The electrophilic fatty-acid derivatives discussed in this work are naturally occurring products of redox reactions and enzymatic activity. Furthermore, several of these electrophilic species and their derivatives represent potential therapeutic candidates.
Probing-Based Estimation of End-to-End Available Bandwidth (2004)

A new mechanism to estimate available bandwidth for multiple hop routes is proposed based on a minimally backlogging concept. Since the proposed mechanism can estimate the available bandwidth quickly and track it adaptively, a reasonable range of available bandwidth for a short time interval can be obtained using the mean and variance of the estimated available bandwidth. The performance of the proposed mechanism is verified by simulation in a multiple hop network topology.
Biochemical markers of joint tissue turnover in early rheumatoid arthritis. (2004)

The progression of rheumatoid arthritis (RA), a disease characterized by synovitis, cartilage degradation and bone erosion, is highly variable from patient to patient. New specific biological markers reflecting quantitative and dynamic changes in joint tissue turnover have been recently developed and include assays for type II collagen synthesis and degradation and synovitis. Increasing evidence from prospective studies in early RA indicate that some of these markers may be useful to predict the progression and identify patients at risk for rapid joint damage, before any damage is detected by radiography. Although studies on their value in assessing the efficacy of treatments are still limited, preliminary data in early RA suggest that biological markers will play an important role in the development and the early monitoring of disease modifying antirheumatic drugs with respect to future radiographic progression.
Retinoids and related compounds. Part 20.1 Synthesis of (11Z)-8,18-ethanoretinal and a conformational study of the rhodopsin chromophore (1997)

In order to investigate the conformation of the chromophore around the trimethylcyclohexene ring in rhodopsin, (11Z)-8,18-ethanoretinal 6 has been synthesized. Its binding experiment with bovine opsin afforded a new rhodopsin analogue, the opsin shift and CD spectrum of which were similar to those of natural rhodopsin. These experimental results strongly suggest that the torsional angle around the 6–7 single bond in rhodopsin corresponds to the torsional angle in (11Z)-8,18-ethanoretinal 6. In addition, MMX calculations for 2 and 6 have been carried out and are reported.
Humanising the mouse genome piece by piece (2019)

To better understand human health and disease, researchers create a wide variety of mouse models that carry human DNA. With recent advances in genome engineering, the targeted replacement of mouse genomic regions with orthologous human sequences has become increasingly viable, ranging from finely tuned humanisation of individual nucleotides and amino acids to the incorporation of many megabases of human DNA. Here, we examine emerging technologies for targeted genomic humanisation, we review the spectrum of existing genomically humanised mouse models and the insights such models have provided, and consider the lessons learned for designing such models in the future.