gebhart/patrepeval huggingface dataset:
Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo (1991)

We have compared the adhesion of 51Cr-labeled eosinophils and neutrophils to cultured human umbilical vein endothelial cell (EC) monolayers that have been stimulated with IL-1, TNF, or LPS. Each agent stimulated the adhesion to EC of both eosinophils and neutrophils in a similar dose- and time-dependent manner. F(ab')2 fragments of mAb 1.2B6 (anti-endothelial leukocyte adhesion molecule (ELAM)-1) and mAb 6.5B5 (anti-intercellular adhesion molecule (ICAM)-1) each inhibited partially, and to a similar extent, eosinophil and neutrophil adhesion to EC monolayers prestimulated with TNF (10 ng/ml) for 6 h. Greater inhibition of both eosinophil and neutrophil adhesion was achieved by combining the effects of mAb 1.2B6 with either mAb 6.5B5 or mAb TS1/18 (anti-CD18). These observations indicate that both ELAM-1 and ICAM-1 are involved in the adhesion of eosinophils and neutrophils to EC stimulated with TNF. In order to determine whether these molecules are expressed in vivo during allergen-induced late phase allergic responses in the skin, human skin biopsies were examined at 6 h after Ag or saline challenge with the use of an alkaline phosphatase-staining technique. Both ELAM-1 and ICAM-1 were expressed with greater intensities in Ag-challenged biopsies, suggesting that these molecules may be involved in granulocyte recruitment in vivo. The similarities we have established between mechanisms of eosinophil and neutrophil adhesion to cytokine-stimulated EC suggests that factors other than differential leukocyte-EC adhesion may be responsible for the selective accumulation of eosinophils at sites of allergic inflammation.
Reduced cytosolic acidification during exercise suggests defective glycolytic activity in skeletal muscle of patients with Becker muscular dystrophy (1999)

Becker muscular dystrophy is an X-linked disorder due to mutations in the dystrophin gene, resulting in reduced size and/or content of dystrophin. The functional role of this subsarcolemma protein and the biochemical mechanisms leading to muscle necrosis in Becker muscular dystrophy are still unknown. In particular, the role of a bioenergetic deficit is still controversial. In this study, we used 31p magnetic resonance spectroscopy (31p-MRS) to investigate skeletal muscle mitochondrial and glycolytic ATP production in vivo in 14 Becker muscular dystrophy patients. Skeletal muscle glycogenolytic ATP production, measured during the first minute of exercise, was similar in patients and controls. On the other hand, during later phases of exercise, skeletal muscle in Becker muscular dystrophy patients was less acidic than in controls, the cytosolic pH at the end of exercise being significantly higher in Becker muscular dystrophy patients. The rate of proton efflux from muscle fibres of Becker muscular dystrophy patients was similar to that of controls, pointing to a deficit in glycolytic lactate production as a cause of higher end-exercise cytosolic pH in patients. The maximum rate of mitochondrial ATP production was similar in muscle of Becker muscular dystrophy patients and controls. The results of this in vivo 31P-MRS study are consistent with reduced glucose availability in dystrophin-deficient muscles.
Ester formation by alcohol acetyltransferase from brewers' yeast. (1981)

Alcohol acetyltransferase responsible for the formation of acetate esters during beer fermentation was found to be localized at the cell membrane of brewers' yeast. This cell membrane-bound enzyme was purified 120-fold by solubilization with Triton X-100, gel filtration on a Sepharose 6B column and chromatography on a DEAE-Sephadex A-50 column. The enzyme was most active at 30°C at pH 78. It was least active against C3 alcohol among C1C6 alcohols, and slightly more active against straight-chain alcohols than against branched-chain alcohols with the same carbon number. The enzyme was strongly inhibited by unsaturated fatty acids, heavy metal ions and sulfhydryl reagents.
Single-cell profiling reveals that eRNA accumulation at enhancer–promoter loops is not required to sustain transcription (2016)

Enhancers are intergenic DNA elements that regulate the transcription of target genes in response to signaling pathways by interacting with promoters over large genomic distances. Recent studies have revealed that enhancers are bi-directionally transcribed into enhancer RNAs (eRNAs). Using single-molecule fluorescence in situ hybridization (smFISH), we investigated the eRNA-mediated regulation of transcription during estrogen induction in MCF-7 cells. We demonstrate that eRNAs are localized exclusively in the nucleus and are induced with similar kinetics as target mRNAs. However, eRNAs are mostly nascent at enhancers and their steady-state levels remain lower than those of their cognate mRNAs. Surprisingly, at the single-allele level, eRNAs are rarely co-expressed with their target loci, demonstrating that active gene transcription does not require the continuous transcription of eRNAs or their accumulation at enhancers. When co-expressed, sub-diffraction distance measurements between nascent mRNA and eRNA signals reveal that co-transcription of eRNAs and mRNAs rarely occurs within closed enhancer-promoter loops. Lastly, basal eRNA transcription at enhancers, but not E2-induced transcription, is maintained upon depletion of MLL1 and ERα, suggesting some degree of chromatin accessibility prior to signal-dependent activation of transcription. Together, our findings suggest that eRNA accumulation at enhancer-promoter loops is not required to sustain target gene transcription.
Development of a Binding Model to Protein Tyrosine Kinases for Substituted Pyrido[2,3-d]pyrimidine Inhibitors (1998)

Previously, our laboratories have reported on a new class of highly potent tyrosine kinase inhibitors based on the pyrido[2, 3-d]pyrimidine core template. To understand the structural basis for the potency and specificity, a model for the binding mode of this class of inhibitors to the tyrosine kinase domains of c-Src, PDGFr, FGFr, and EGFr tyrosine kinases was developed from structural information (principally utilizing the catalytic domain of c-AMP-dependent protein kinase as template) and structure-activity relationship (SAR) information. In the resulting docking mode, the pyrido[2,3-d]pyrimidine template shows a hydrogen-bonding pattern identical to that of olomoucine. The 6-aryl substituent of the heterocycle is located deep in the binding cleft in a pocket not used by ATP, which helps to confer high-affinity binding as well as specificity. The 2-anilino and 2-(dialkylamino)alkylamino substituents as well as the 7-urea substituent of inhibitors within this class are located at the entrance of the binding cleft and make contact with residues in the hinge region between the two kinase lobes. This allows considerable variability and bulk tolerance for C-2 and N-7 substituents. The models presented here are consistent with the SAR seen for the inhibition of a number of isolated enzymes and provide a structural basis to explain their specificity. They have been used successfully to design new highly potent protein kinase inhibitors.
Achieving the Rayleigh Limit in Fresnel Incoherent Correlation Holographic 3D Fluorescence Microscopy (2011)

Fresnel Incoherent Correlation Holography (FINCH) enables 3D images to be created from incoherent light with just a camera and spatial light modulator. High resolution fluorescence microscopy at the Rayleigh optical limit will be demonstrated.
Calcitonin gene‐related peptide‐immunoreactive nerves in the rat kidney (1991)

Cryostat- and vibratome-cut rat kidney secretions were singly or doubly labeled to visualize immunoreactive calcitonin-gene-related peptide (CGRPI) and substance P (SPI). Rats were perfused with 2-4% paraformaldehyde + 0.15% picric acid then rinsed with buffer. Horseradish peroxidase (HRP) was used to visualize CGRP in vibratome sections, and combined HRP and fluorophore were used to visualize the two peptides simultaneously in cryostat sections. There is a complex, multilayered plexus of CGRP nerves on the renal pelvis and a less dense, single-layered plexus on the major branches of the renal artery and on interlobar arteries and veins. A few axons innervate finer branches of the arterial tree and other intrarenal structures. Results of double immunolabeling suggest that SPI axons comprise a subpopulation of the CGRP axon population in the rat kidney. There was no evidence for a separate population of SPI axons.
Immobilized Affinity Ligand Techniques (1992)

The Matrix. Activation Methods. Immobilization of Ligands. Techniques of the Trade. Selected Applications. Chapter References. Index.
A 10-GHz frequency-domain fluorometer (1990)

We describe the design and performance of a 10-GHz harmonic-content frequency-domain fluorometer. The modulated excitation is provided by the harmonic content of a train of ps pulses. High-speed and/or high-frequency detection was attained with a triode-type microchannel plate photomultiplier tube (MCP PMT) from Hamamatsu, R-2566-6, with 6 μm channels. To minimize the cost of the electronic components, and to minimize the noise due to these components, the detection circuits consists of two frequency ranges, 10 MHz–2 GHz and 2–10 GHz. The upper frequency limit of 10 GHz is determined by the current MCP PMT, so the usual configuration includes a low-noise 2–10-GHz amplifier. This amplifier is easily replaced with a 2–18-GHz amplifier to allow operation to 18 GHz and the use of faster PMTs, should they become available in the future. Measurement of known optical delays demonstrates the accuracy of the instrument. For instance, a 1.69 ps optical delay was measured as 1.7±0.4 ps from 0.5 to 10 GHz, and 1.7±0.2 ps from 2 to 8 GHz, where the uncertainty indicates the maximum deviation from the expected value. The data were shown to be free of systematic errors by measurements on fluorophores with single exponential decays, with decay times ranging from 61 ps to 1.24 ns. Measurement of anisotropy decays with correlation times of 24 ps are shown and it is predicted that correlation times as short as 1 ps could be measured with this instrument. And finally, the sensitivity of the instrumentation was demonstrated by measurements of the very weak intrinsic tryptophan emission of deoxyhemoglobin, which displays decay times ranging from 2 to 820 ps.
Androgen deprivation induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells. (2001)

Early administration of hormonal therapy after failure of first-line treatment is associated with a profound clonal selection of aggressive AI variants, such as CL-1 and CL-2 lines. These tumor lines, with their parental counterparts, can serve as valuable tools for studying the cellular and molecular mechanisms of CaP progression and metastasis under hormonal therapy. CL-1 and CL-2 offer a unique and reproducible model for the evaluation of drug sensitivity and for other therapeutic modalities for advanced prostate cancer.
Peptides on phage: a vast library of peptides for identifying ligands. (1990)

We have constructed a vast library of peptides for finding compounds that bind to antibodies and other receptors. Millions of different hexapeptides were expressed at the N terminus of the adsorption protein (pIII) of fd phage. The vector fAFF1, derived from the tetracycline resistance-transducing vector fd-tet, allows cloning of oligonucleotides in a variety of locations in the 5' region of gene III. A library of 3 x 10(8) recombinants was generated by cloning randomly synthesized oligonucleotides. The library was screened for high-avidity binding to a monoclonal antibody (3-E7) that is specific for the N terminus of beta-endorphin (Tyr-Gly-Gly-Phe). Fifty-one clones selected by three rounds of the affinity purification technique called panning were sequenced and found to differ from previously known ligands for this antibody. The striking finding is that all 51 contained tyrosine as the N-terminal residue and that 48 contained glycine as the second residue. The binding affinities of six chemically synthesized hexapeptides from this set range from 0.35 microM (Tyr-Gly-Phe-Trp-Gly-Met) to 8.3 microM (Tyr-Ala-Gly-Phe-Ala-Gln), compared with 7.1 nM for a known high-affinity ligand (Tyr-Gly-Gly-Phe-Leu). These results show that ligands can be identified with no prior information concerning antibody specificity. Peptide libraries are also likely to be useful in finding ligands that bind to other classes of receptors and in discovering pharmacologic agents.
Microbial Synthesis of Pinene (2014)

The volumetric heating values of today's biofuels are too low to power energy-intensive aircraft, rockets, and missiles. Recently, pinene dimers were shown to have a volumetric heating value similar to that of the tactical fuel JP-10. To provide a sustainable source of pinene, we engineered Escherichia coli for pinene production. We combinatorially expressed three pinene synthases (PS) and three geranyl diphosphate synthases (GPPS), with the best combination achieving ~28 mg/L of pinene. We speculated that pinene toxicity was limiting production; however, toxicity should not be limiting at current titers. Because GPPS is inhibited by geranyl diphosphate (GPP) and to increase flux through the pathway, we combinatorially constructed GPPS-PS protein fusions. The Abies grandis GPPS-PS fusion produced 32 mg/L of pinene, a 6-fold improvement over the highest titer previously reported in engineered E. coli. Finally, we investigated the pinene isomer ratio of our pinene-producing microbe and discovered that the isomer profile is determined not only by the identity of the PS used but also by the identity of the GPPS with which the PS is paired. We demonstrated that the GPP concentration available to PS for cyclization alters the pinene isomer ratio.
Identifying Genes Regulated in a Myc-dependent Manner (2002)

The c-myc proto-oncogene can direct a diverse array of biological activities, including cell cycle progression, apoptosis, and differentiation. It is believed that Myc can affect this wide variety of activities by functioning as a regulator of gene transcription, although few targets have been identified to date. To delineate the molecular program regulated downstream of Myc, we used a cDNA microarray approach and identified 52 putative targets out of >6000 cDNAs analyzed. To further distinguish the subset of genes whose regulation was dependent upon Myc per se from those regulated in response to activation of general mitogenic or apoptotic programs, the putative cDNA targets were then screened by a series of assays. By this approach 37 putative targets were ruled out and 15 Myc target genes were uncovered. Interestingly, comparing our results with other high throughput screens reveals that certain putative Myc targets previously reported are shown not to be regulated downstream of Myc (e.g. ribosomal proteins, HSP90beta), whereas others are further supported by our analyses (e.g. pdgfbetar, nucleolin). The identity of genes specifically regulated downstream of Myc provides the critical tools required to understand the role Myc holds in the transformation process and to delineate how Myc functions as a regulator of gene transcription.
A review on mucoadhesive polymer used in nasal drug delivery system (2011)

This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drug delivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies.
CanaryAdvisor: a statistical-based tool for canary testing (demo) (2015)

Canary testing is an emerging technique that offers to minimize the risk of deploying a new version of software. It does so by slowly transferring load from the current to the new ("canary") version. As this ramp-up progresses, a human compares the performance and correctness of the two versions, and assesses whether to abort the canary version. For canary testing to be effective, a plethora of metrics must be analyzed, including CPU utilization and logged errors, across hundreds to thousands of machines. Performing this analysis manually is both time consuming and error prone. In this paper, we present CanaryAdvisor, a tool for automatic canary testing of cloud-based applications. CanaryAdvisor continuously monitors the deployed versions of an application and detects degradations in correctness, performance, and/or scalability. We describe our design and implementation of the CanaryAdvisor and outline open challenges.
5-Iminodaunorubicin. Reduced cardiotoxic properties in an antitumor anthracycline (1979)

Treatment of daunorubicin with methanolic ammonia affords 5-iminodaunorubicin, the first quinone-modified analogue of either daunorubicin or adriamycin. This product retains antileukemic activity in mice, is less cardiotoxic by electrocardiographic measurements in rats, and is nonmutagenic in Salmonella typhimurium (Ames test).
Synthesis and Electrochemical Properties of Single-Crystal V2O5 Nanorod Arrays by Template-Based Electrodeposition (2004)

This paper reports a study on template-growth and electrochemical properties of single-crystal vanadium pentoxide (V2O5) nanorod arrays from VOSO4 aqueous solution using electrochemical deposition. Uniformly sized vanadium oxide nanorods with a length of about 10 μm with diameters ranging from 100 to 200 nm were grown over a large area with near unidirectional alignment. These nanorods have single-crystalline structure with a growth direction of [010]. Electrochemical property analysis indicates that nanorod array electrodes have significantly higher current density and energy storage density than sol−gel-derived V2O5 films.
Learned in Translation: Contextualized Word Vectors (2017)

Computer vision has benefited from initializing multiple deep layers with weights pretrained on large supervised training sets like ImageNet. Natural language processing (NLP) typically sees initialization of only the lowest layer of deep models with pretrained word vectors. In this paper, we use a deep LSTM encoder from an attentional sequence-to-sequence model trained for machine translation (MT) to contextualize word vectors. We show that adding these context vectors (CoVe) improves performance over using only unsupervised word and character vectors on a wide variety of common NLP tasks: sentiment analysis (SST, IMDb), question classification (TREC), entailment (SNLI), and question answering (SQuAD). For fine-grained sentiment analysis and entailment, CoVe improves performance of our baseline models to the state of the art.
Electrophysiological actions of nicotine on substantia nigra single units (1985)

Extracellular recordings of single unit activity were made in the substantia nigra (SN) of chloral hydrate-anaesthetized rats. Dopaminergic neurones of the pars compacta (SNC) were stimulated by (-)-nicotine bitartrate (1.0 mg kg-1) given subcutaneously (s.c.). This action was prevented by the secondary amine mecamylamine HCl (2.0 mg kg-1 i.v.) but not by a ganglion-blocking dose of the bisquaternary compound chlorisondamine Cl (0.1 mg kg-1 i.v.). Mecamylamine reduced the spontaneous activity of dopaminergic neurones. Nicotine, when administered intravenously (2-128 micrograms kg-1 cumulative dose), also stimulated dopamine cells and this action was dose-related. Nicotine, administered intravenously, (2-128 micrograms kg-1 cumulative dose) markedly excited non-dopamine cells in the pars reticulata (SNR) in a dose-related manner. In rats pretreated with chlorisondamine (0.1 mg kg-1 i.v.), nicotine induced a small excitatory or depressant action, but the marked excitation was not seen. Mecamylamine (2 mg kg-1 i.v.) completely prevented the actions of nicotine. The results are consistent with a direct excitatory action of nicotine on dopaminergic neurones of the substantia nigra pars compacta. The pronounced excitatory action of systemically administered nicotine on non-dopamine cells of the pars reticulata appears to be of peripheral origin.
Electron kinetics and non-Joule heating in near-collisionless inductively coupled plasmas (1997)

Electron kinetics in an inductively coupled plasma sustained by a coaxial solenoidal coil is studied for the near-collisionless regime when the electron mean free path is large compared to the tube radius. Emphasis is placed on the influence of the oscillatory magnetic field induced by the coil current and the finite dimension of the plasma on electron heating and formation of the electron distribution function (EDF). A nonlocal approach to the solution of the Boltzmann equation is developed for the near-collisionless regime when the traditional two-term Legendre expansion for the EDF is not applicable. Dynamic Monte Carlo (DMC) simulations are performed to calculate the EDF and electron heating rate in argon in the pressure range 0.3--10 mTorr and driving frequency range 2--40 MHz, for given distributions of electromagnetic fields. The wall potential ${\mathrm{\ensuremath{\varphi}}}_{\mathrm{w}}$ in DMC simulations is found self-consistently with the EDF. Simulation results indicate that the EDF of trapped electrons with total energy \ensuremath{\varepsilon}${\mathrm{\ensuremath{\varphi}}}_{\mathrm{w}}$ is almost isotropic and is a function solely of \ensuremath{\varepsilon}, while the EDF of untrapped electrons with \ensuremath{\varepsilon}&gt;e${\mathrm{\ensuremath{\varphi}}}_{\mathrm{w}}$ is notably anisotropic and depends on the radial position. These results are in agreement with theoretical analysis.
Golden Mandarin (II)-an improved single-chip real-time Mandarin dictation machine for Chinese language with very large vocabulary (1993)

Golden Mandarin (II) is an improved single-chip real-time Mandarin dictation machine with a very large vocabulary for the input of unlimited Chinese sentences into computers using voice. In this dictation machine only a single-chip Motorola DSP 96002D on an Ariel DSP-96 card is used, with a preliminary character correct rate of around 95% in speaker-dependent mode at a speech of 0.36 s per character. This is achieved by many new techniques, primarily a segmental probability modeling technique for syllable recognition especially considering the characteristics of Mandarin syllables, and a word-lattice-based Chinese character bigram for character identification especially considering the structure of the Chinese language.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A review of Neuropathic Pain: From Guidelines to Clinical Practice (2017)

Pfizer, Italy.
Hits and misses of a great mind (1993)

John von Neumann was undoubtedly one of the great minds of the twentieth century. It is something of a scandal that there has been no biography until now – almost 40 years after his death. The author, Norman Macrae, is to be commended for his initiative (or should it be bravery?) in undertaking this mission.