gebhart/patrepeval huggingface dataset:
Tyrosine phosphorylation is involved in reorganization of the actin cytoskeleton in response to serum or LPA stimulation (1994)

Tyrosine phosphorylation is known to regulate the formation of focal adhesions in cells adhering to extracellular matrix (ECM). We have investigated the possible involvement of tyrosine phosphorylation and the focal adhesion kinase (FAK) in the cytoskeletal changes induced by serum or lysophosphatidic acid (LPA) in quiescent Swiss 3T3 fibroblasts. As shown previously by others, quiescent cells stimulated with serum or LPA reveal a rapid reappearance of focal adhesions and stress fibers. Here we show that this is accompanied by an increase in phosphotyrosine in focal adhesions and specifically an increase in the tyrosine phosphorylation of FAK. The LPA-stimulated reappearance of focal adhesions and stress fibers is blocked by inhibitors of phospholipase C but not by pertussis toxin (PTX), indicating that this LPA signaling pathway is mediated by phospholipase C activation and does not involve PTX-sensitive G proteins. In the absence of serum or LPA, these cytoskeletal effects and the tyrosine phosphorylation of FAK can be mimicked by sodium orthovanadate in conjunction with hydrogen peroxide, agents that inhibit protein tyrosine phosphatases and thereby elevate levels of phosphotyrosine. Two tyrosine kinase inhibitors, erbstatin and genistein block both the serum-induced tyrosine phosphorylation of FAK and the assembly of focal adhesions and stress fibers. Two other tyrosine kinase inhibitors, tyrphostins 47 and 25, previously shown to inhibit FAK, failed to prevent FAK phosphorylation or the reassembly of focal adhesions and stress fibers in response to serum. However, these inhibitors did prevent FAK phosphorylation and cytoskeletal assembly in response to lysophosphatidic acid (LPA), one component of serum previously shown to stimulate assembly of focal adhesions and stress fibers. Our findings suggest that the response to serum is complex and that although FAK phosphorylation is important, other tyrosine kinases may also be involved.
mRNA knockdown by single strand RNA is improved by chemical modifications (2012)

While RNAi has traditionally relied on RNA duplexes, early evaluation of siRNAs demonstrated activity of the guide strand in the absence of the passenger strand. However, these single strands lacked the activity of duplex RNAs. Here, we report the systematic use of chemical modifications to optimize single-strand RNA (ssRNA)-mediated mRNA knockdown. We identify that 2'F ribose modifications coupled with 5'-end phosphorylation vastly improves ssRNA activity both in vitro and in vivo. The impact of specific chemical modifications on ssRNA activity implies an Ago-mediated mechanism but the hallmark mRNA cleavage sites were not observed which suggests ssRNA may operate through a mechanism beyond conventional Ago2 slicer activity. While currently less potent than duplex siRNAs, with additional chemical optimization and alternative routes of delivery, chemically modified ssRNAs could represent a powerful RNAi platform.
Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties (2013)

A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition.
Distributed-and-split data-control extension to SCSI for scalable storage area networks (2003)

A "storage-area network" (SAN) comprises computers ("initiators"), storage "block devices" ("targets"), and a controller(s). Most SANs use the SCSI protocol over various communication infrastructures. Presently, all initiator-target traffic must pass through the controller, severely limiting scalability. We extend the SCSI-3 transport layer to support distribution, and combine this with SCSIs support for data-control split to create DSDC, a novel architecture that can be used over any networking infrastructure: data may be sent directly between initiators and targets, relieving the controller communication bottleneck; the use of multiple paths for data moreover relieves traffic bottlenecks on network links; finally, passing all commands through the Controller retains simplicity. DSDC thus enables the construction of much larger SANs while retaining the simplicity of a single controller. A prototype SAN using Ethernet and Linux nodes, with DSDC implemented in the iSCSI transport layer protocol and in the controller's SCSI application layer, has been constructed.
Repair of triple helix directed psoralen adducts in human cells (1994)

Triple helix forming oligonucleotides can direct DNA damaging agents at specific sites in an intact double helix. In our study, triple helix formation was demonstrated in a SV40 based shuttle vector treated with psoralen linked to a 22-mer purine rich oligonucleotide. UVA irradiation caused a covalent linkage of the oligonucleotide through the psoralen to the mutational supF marker gene of the plasmid. After passage in the Jurkat human cell line the recovered vector was analysed in an indicator bacterial strain and mutants were collected. The presence of adducts in the target sequence did not reduce the yield of replicated progeny vector molecules, indicating repair of triple helix associated monoadducts and cross-links. Mutations were highly targeted to a six nucleotide long region of the target sequence. The number of target sequence mutants obtained after triple helix directed psoralen treatment was approximately 160 times higher than with free psoralen. A further investigation of the exact mechanism of the mutational process could make triple helix directed mutagenesis a more useful tool in gene therapy, antiviral therapy, and in studies on DNA repair and genome organisation.
Fc receptor modulation in mononuclear phagocytes maintained on immobilized immune complexes occurs by diffusion of the receptor molecule. (1983)

We describe a method for synchronously assembling antigen-antibody complexes underneath macrophages adherent to an antigen-coated surface. We have used this method to study the mechanism of Fc receptor (FcR) disappearance that occurs when resident and thioglycollate-elicited mouse macrophages are cultured on immune complex-coated surfaces. Erythrocytes opsonized with IgG (E(IgG) and a monoclonal antibody (2.4G2 IgG) directed against the trypsin-resistant FcR (FcRII) were used as indicators of the presence and distribution of FcRII molecules on the macrophage plasma membrane. Inhibitors of aerobic (NaCN) and anerobic (2-deoxyglucose, NaF) glycolysis and pinocytosis, of protein biosynthesis (cycloheximide), and of cytoskeletal function (cytochalasin B and D, colchicine, podophyllotoxin, taxol) did not reduce the rate or extent of FcRII modulation. Moreover, treatment of the macrophages with 0.1-0.5% formaldehyde did not reduce the extent of FcRII modulation as measured by the disappearance of E(IgG) binding sites. FcRII modulation was markedly slowed when the temperature was decreased to 2-4 degrees C. These results prove that FcRII modulation is governed by diffusion of the receptor in the plasma membrane. From the speed of FcRII disappearance from the macrophage's upper surface we calculate that the receptor has a diffusion coefficient at 37 degrees C of 2.5 X 10(-9) cm2/s. This finding indicates that FcRII, in its unligated form, is not linked to the macrophage's cytoskeleton, and that the receptor is capable of accommodating spatially to any distribution of ligands on a particle's surface.
Permeation through cornea. (2001)

The permeability of the cornea to drugs is clinically important because it is the major factor determining the efficacy of topically applied ophthalmic preparations. With this perspective, the present article gives a brief update and overview of corneal structure and proposed mechanisms of permeation. Physiological, physicochemical and formulation factors affecting drug permeation through cornea are highlighted. Influence of ocular penetration enhancers on drug permeation is also discussed.
DAISY, an adaptive, knowledge-based driver monitoring and warning system (2005)

This paper presents an intelligent monitoring and warning aid for the driver on German motorways. Haptic warning messages are generated and initiated on the basis of comprehensive system knowledge about the driving situation including the behavioural state and the condition of the driver. The warning messages are adapted to the individual driving style of the person actually driving. Experiments have been conducted with the system in a driving simulator and in a test vehicle with encouraging results in support of the system concept. This development was part of the PROMETHEUS project.
The mechanism by which epidermal growth factor inhibits glycogen synthase kinase 3 in A431 cells (1994)

Glycogen synthase kinase 3 (GSK3) was inhibited by 50% within 5 min when A431 cells were stimulated with epidermal growth factor (EGF). The inhibition was unaffected by rapamycin at concentrations which blocked the activation of p70 S6 kinase, and reversed by incubation with protein phosphatase-1. EGF stimulation of A431 cells inhibited GSK3 alpha and GSK3 beta to a similar extent, and inhibition was accompanied by phosphorylation of the tryptic peptides containing the serine residues phosphorylated in vitro by p70 S6 kinase or MAP kinase-activated protein (MAPKAP) kinase-1 beta (also termed Rsk-2). These results demonstrate that EGF inhibits GSK3 by inducing phosphorylation of a serine residue and that GSK3 is not phosphorylated in vivo by either p70 S6 kinase or protein kinase C.
Thermodynamic and Kinetic Framework of Selenocysteyl-tRNASec Recognition by Elongation Factor SelB (2009)

SelB is a specialized translation elongation factor that delivers selenocysteyl-tRNA(Sec) (Sec-tRNA(Sec)) to the ribosome. Here we show that Sec-tRNA(Sec) binds to SelB.GTP with an extraordinary high affinity (K(d) = 0.2 pm). The tight binding is driven enthalpically and involves the net formation of four ion pairs, three of which may involve the Sec residue. The dissociation of tRNA from the ternary complex SelB.GTP.Sec-tRNA(Sec) is very slow (0.3 h(-1)), and GTP hydrolysis accelerates the release of Sec-tRNA(Sec) by more than a million-fold (to 240 s(-1)). The affinities of Sec-tRNA(Sec) to SelB in the GDP or apoforms, or Ser-tRNA(Sec) and tRNA(Sec) to SelB in any form, are similar (K(d) = 0.5 microm). Thermodynamic coupling in binding of Sec-tRNA(Sec) and GTP to SelB ensures at the same time the specificity of Sec- versus Ser-tRNA(Sec) selection and rapid release of Sec-tRNA(Sec) from SelB after GTP cleavage on the ribosome. SelB provides an example for the evolution of a highly specialized protein-RNA complex toward recognition of unique set of identity elements. The mode of tRNA recognition by SelB is reminiscent of another specialized factor, eIF2, rather than of EF-Tu, the common delivery factor for all other aminoacyl-tRNAs, in line with a common evolutionary ancestry of SelB and eIF2.
Novel approaches for identifying target antigens of autoreactive human B and T cells (2009)

Antigen-specific immune responses in multiple sclerosis have been studied for decades, but the target antigens of the putatively autoaggressive B and T cells still remain elusive. Here, we summarize recent strategies which are based on the direct analysis of biopsy or autopsy specimens from patients. Since this material is extremely scarce, the experimental methods need to be exceptionally sensitive. We describe technologies to distinguish (auto) aggressive T cells from irrelevant bystander lymphocytes by analyzing clonal expansions in relation to the morphological location of the cells in the tissue lesions. We then discuss approaches to clone matching alpha- and beta-chains of the antigen-specific T cell receptor (TCR) molecules from single T cells. This is necessary because usually, several clones are expanded and are diluted by many irrelevant cells. The matching TCR chains from individual T cells can be resurrected in hybridoma cells which may then be used for antigen searches. We discuss strategies to identify antigens of gammadelta- and alphabeta-TCR molecules, such as biochemical methods, candidate antigens, human leukocyte antigen requirements, synthetic peptide, and cDNA libraries. These strategies are tailored to characterize the antigens of the membrane-anchored, low-affinity TCR molecules. The strategies to identify (auto) reactive B cells or immunoglobulin (Ig) molecules are fundamentally different, because Ig molecules are water-soluble and have high affinities. We further discuss proteome-based approaches, techniques that analyze Ig-chains from single B cells, and a repertoire-based method that compares Ig-proteomes and Ig-transcriptomes. The first method detects Ig antigens directly, whereas the latter two methods allow reconstruction of Ig molecules, which can be used for antigen searches.
Transglutaminase-Catalyzed Site-Specific Conjugation of Small-Molecule Probes to Proteins in Vitro and on the Surface of Living Cells (2006)

Site-specific protein labeling methods allow cell biologists to access the vast array of existing chemical probes for the study of specific proteins of interest in the live cell context. Here we describe the use of the transglutaminase enzyme from guinea pig liver (gpTGase), whose natural function is to cross-link glutamine and lysine side chains, to covalently conjugate various small-molecule probes to recombinant proteins fused to a 6- or 7-amino acid transglutaminase recognition sequence, called a Q-tag. We demonstrate labeling of Q-tag fusion proteins both in vitro and on the surface of living mammalian cells with biotin, fluorophores, and a benzophenone photoaffinity probe. To illustrate the utility of this labeling, we tagged the NF-kappaB p50 transcription factor with benzophenone, cross-linked with UV light, and observed increased levels of p50 homodimerization in the presence of DNA and the binding protein myotrophin.
Giant volume magnetostriction in the FeRh alloy (1994)

In a search for high-magnetostrictive materials we have discovered in FeRh a large induced volume magnetostriction (\ensuremath{\approxeq}0.82%) at and above room temperature. Thermal-expansion measurements performed on the ordered CsCl crystallographic structure of FeRh in the temperature range 250--800 K reveal Invar-like behavior at ${\mathit{T}}_{\mathit{c}}$=680 K associated with a paramagnetic-ferromagnetic second-order phase transition. At ${\mathit{T}}_{\mathrm{F}\mathrm{\ensuremath{-}}\mathrm{AF}}$=405 K, a large contraction of the lattice within the ferromagnetic (F) phase takes place through a first-order transformation resulting in a low-volume, low-temperature antiferromagnetic phase (AF) (anti-invar-like behavior). At moderate fields above room temperature and within the AF phase, we have found a giant value for the volume magnetostriction of \ensuremath{\omega}=8.2\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}3}$. These results constitute evidence for the existence of the theoretically predicted metastable F phase (high-volume state) within the AF phase which can be reached by an applied magnetic field. The present experiments offer additional perspectives on an old problem in magnetism and suggest potential applications of this alloy as a high-magnetostrictive material.
Analysis of picosecond pulse shape synthesis by spectral masking in a grating pulse compressor (1986)

This paper analyzes the synthesis of arbitrarily shaped optical pulses by spectral filtering in a fiber-and-grating pulse compressor. Spectral filtering of phase and amplitude is achieved by masking the spatially dispersed frequency components within the compressor. We show that the spectral filter is the convolution of the mask with the beam's transverse intensity profile. We discuss the effect of diffraction from the features of the physical mask, and show how finite spatial resolution limits the range of attainable temporal profiles. The fundamental limitation on spectral resolution is derived. Spectra and temporal pulse shapes corresponding to a variety of physical masks are calculated and are found to be in excellent agreement with experiments done with compressed pulses from a mode-locked Nd: YAG laser.
Anionic metal hydride catalysts. 2. Application to the hydrogenation of ketones, aldehydes, carboxylic acid esters, and nitriles (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnionic metal hydride catalysts. 2. Application to the hydrogenation of ketones, aldehydes, carboxylic acid esters, and nitrilesRoger A. Grey, Guido P. Pez, and Andrea WalloCite this: J. Am. Chem. Soc. 1981, 103, 25, 7536–7542Publication Date (Print):December 1, 1981Publication History Published online1 May 2002Published inissue 1 December 1981https://doi.org/10.1021/ja00415a022RIGHTS & PERMISSIONSArticle Views1953Altmetric-Citations192LEARN 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 InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
The prognostic value of lymphatic and blood vessel invasion in operable breast cancer (1995)

The prevalence of BVI was particularly low in this study, and the question of its possible prognostic role for patients with breast cancer should be assessed with methods that amplify its detection. LVI is a strong prognostic factor for operable patients with breast cancer. In lymph node negative patients, LVI is a predictor of poor prognosis for those who are consequently candidates for adjuvant therapy. Similarly, in lymph node positive patients, LVI is a predictor for a high risk of death for those who are candidates for highly intensive adjuvant strategies.
Label-free Proteomic Reveals that Cowpea Severe Mosaic Virus Transiently Suppresses the Host Leaf Protein Accumulation During the Compatible Interaction with Cowpea (Vigna unguiculata [L.] Walp.) (2016)

Viruses are important plant pathogens that threaten diverse crops worldwide. Diseases caused by Cowpea severe mosaic virus (CPSMV) have drawn attention because of the serious damages they cause to economically important crops including cowpea. This work was undertaken to quantify and identify the responsive proteins of a susceptible cowpea genotype infected with CPSMV, in comparison with mock-inoculated controls, using label-free quantitative proteomics and databanks, aiming at providing insights on the molecular basis of this compatible interaction. Cowpea leaves were mock- or CPSMV-inoculated and 2 and 6 days later proteins were extracted and analyzed. More than 3000 proteins were identified (data available via ProteomeXchange, identifier PXD005025) and 75 and 55 of them differentially accumulated in response to CPSMV, at 2 and 6 DAI, respectively. At 2 DAI, 76% of the proteins decreased in amount and 24% increased. However, at 6 DAI, 100% of the identified proteins increased. Thus, CPSMV transiently suppresses the synthesis of proteins involved particularly in the redox homeostasis, protein synthesis, defense, stress, RNA/DNA metabolism, signaling, and other functions, allowing viral invasion and spread in cowpea tissues.
Evaluating somatic tumor mutation detection without matched normal samples (2017)

A detailed method for somatic mutation detection without matched normal samples enables study of larger numbers of tumor samples, as well as tumor samples for which a matched normal is not available. As sensitivity/recall is similar to tumor/normal mutation detection but precision is lower, tumor-only detection is more appropriate for classification of samples based on known mutations. Although matched tumor-normal analysis is preferred due to higher precision, we demonstrate that mutation detection without matched normal samples is possible for certain applications.
Molecular biology of septic shock. (1998)

Septic shock is a complex pathophysiologic state which often leads to multiple organ dysfunction, multiple organ failure, and death. This review summarizes current views on the molecular biology of three aspects of septic shock: recognition of bacterial invasion and induction of the cytokine response; genetic variability among humans and their predispositions toward pathologic inflammatory responses; and the signal transduction mechanisms which account for the transfer of molecular signals from cytokine receptors on the plasma membrane to cytokine-responsive genes in the nucleus. In particular, the review summarizes the pathway involved in tumor necrosis factor signaling through nuclear factor-kappaB, and elucidates the molecular signals involved in inflammatory responses and apoptosis.
Cleavage of VX Simulants by Micellar Iodoso- and Iodoxybenzoate (1999)

O,S-Diethyl phenylphosphonothioate (5) and S-phenyl (9) and S-ethyl diphenylthiophosphinate (10) were efficiently cleaved by 3-fold excess o-iodosobenzoate (IBA) in aqueous micellar cetyltrimethylammonium chloride solutions at pH 9.5. The maximum observed rate constants (monitored by HPLC aliquot procedures) were 1.09 × 10-3 s-1 for 5 and 6.0 × 10-3 s-1 for 10 with 0.06 M IBA at 25 °C. 9 cleaved too rapidly to follow by the aliquot method. With equimolar quantities of 5 and IBA, cleavage was slower and incomplete because of the reduction of the IBA to iodobenzoate by the EtSH liberated in the cleavage step. Mixtures of IBA and o-iodoxybenzoate (IBX) efficiently cleaved 5, even though IBX was not reactive toward 5, because the IBX competitively oxidized the EtSH, mitigating its reaction with IBA, while simultaneously affording additional IBA as the IBX was reduced. Studies of IBA and IBX redox reactions with EtSH are also included.
Letter (1991)

Dear Editor I am a staff nurse working in an assessment and rehabilitation ward for the care of elderly people. I would like to redesign our noticeboard to include information for patients as well as relatives/clients. Any ideas or information on posters. leaflets, etc, readers can provide me with would be greatly appreciated.
Processing of Adenovirus 2-Induced Proteins (1973)

Analysis of (35)S-methionine-labeled extracts of adenovirus 2-infected KB cells revealed 22 virus-induced polypeptide components. Most proteins of the virion were easily detected in extracts of whole cells labeled for short periods between 15 and 30 h after infection; however, several virion components were conspicuously absent. Radioactivity appeared in two of these virion components during a chase in nonradioactive medium, and this appearance was paralleled by a decrease in the radioactivity associated with two nonvirion adenovirus-induced proteins, results which imply precursor-product relationships for these components. Comparison of one of the chasable adenovirus-induced components (designated P-VII; mass of 20,000 daltons) and the major core protein (VII; mass of 18,500 daltons) of the virion showed that they have four common methionine-containing tryptic peptides; P-VII has an additional methionine residue which is not found in the major core protein. We propose that at least two of the adenovirus 2 virion components are derived by the cleavage of higher molecular weight precursor polypeptides.