gebhart/patrepeval huggingface dataset:
A catalogue of splice junction sequences (1982)

Splice junction sequences from a large number of nuclear and viral genes encoding protein have been collected. The sequence CAAG/GTAGAGT was found to be a consensus of 139 exon-intron boundaries (or donor sequences) and (TC)nNCTAG/G was found to be a consensus of 130 intron-exon boundaries (or acceptor sequences). The possible role of splice junction sequences as signals for processing is discussed.
Domain II Mutants of Pseudomonas Exotoxin Deficient in Translocation (1989)

Pseudomonas exotoxin (PE) kills mammalian cells in a complex process that involves cell surface binding, internalization by endocytosis, translocation to the cytosol, and ADP-ribosylation of elongation factor 2. PE is a three-domain protein in which domain I binds to the cell surface, domain II promotes translocation into the cytosol, and domain III carries out ADP-ribosylation. To determine how translocation occurs, we have mutated all the arginine residues in domain II and found that mutations at positions 276 and 279 greatly diminished the cytotoxicity of PE and mutations 330 and 337 substantially reduced cytotoxicity. Biochemical studies indicate that after internalization into an endocytic compartment, the PE molecule undergoes a specific and saturable intracellular interaction, and this interaction is deficient in an Arg276----Gly mutant. Our data suggest that the translocation process of PE involves a specific interaction of Arg276 (and possibly Arg279, Arg330, and Arg337) with components of an intracellular compartment.
Saccharomyces cerevisiae cho2 mutants are deficient in phospholipid methylation and cross-pathway regulation of inositol synthesis. (1988)

Five allelic Saccharomyces cerevisiae mutants deficient in the methylation of phosphatidylethanolamine (PE) have been isolated, using two different screening techniques. Biochemical analysis suggested that these mutants define a locus, designated CHO2, that may encode a methyltransferase. Membranes of cho2 mutant cells grown in defined medium contain approximately 10% phosphatidylcholine (PC) and 40-50% PE as compared to wild-type levels of 40-45% PC and 15-20% PE. In spite of this greatly altered phospholipid composition, cho2 mutant cells are viable in defined medium and are not auxotrophic for choline or other phospholipid precursors such as monomethylethanolamine (MME). However, analysis of yeast strains carrying more than one mutation affecting phospholipid biosynthesis indicated that some level of methylated phospholipid is essential for viability. The cho2 locus was shown by tetrad analysis to be unlinked to other loci affecting phospholipid synthesis. Interestingly, cho2 mutants and other mutant strains that produce reduced levels of methylated phospholipids are unable to properly repress synthesis of the cytoplasmic enzyme inositol-1-phosphate synthase. This enzyme was previously shown to be regulated at the level of mRNA abundance in response to inositol and choline in the growth medium. We cloned the CHO2 gene on a 3.6-kb genomic DNA fragment and created a null allele of cho2 by disrupting the CHO2 gene in vivo. The cho2 disruptant, like all other cho2 mutants, is viable, exhibits altered regulation of inositol biosynthesis and is not auxotrophic for choline or MME.
Elastic scattering spectroscopy as a diagnostic tool for differentiating pathologies in the gastrointestinal tract: preliminary testing (1996)

We report preliminary clinical testing of elastic-scattering spectroscopy for the detection of pathologies of the gastrointestinal tract. Tissue pathologies are detected and diagnosed using spectral measurements of elastically scattered light in an optical geometry that results in sensitivity to both the absorption and scattering properties of the tissue, over a wide range of wavelengths (300 to 750 nm). The system employs a small fiber optic probe, which is amenable to use with most endoscopes or catheters, or to direct surface examination, as well as interstitial needles. In this paper we report the results of preliminary clinical measurements on various organ sites of the gastrointestinal tract. In several instances the data indicate promise for this diagnostic method to distinguish malignant and dysplastic conditions from normal or other diagnoses.
Electrochemical Quantitation of DNA Immobilized on Gold (1998)

We have developed an electrochemical method to quantify the surface density of DNA immobilized on gold. The surface density of DNA, more specifically the number of nucleotide phosphate residues, is calculated from the amount of cationic redox marker measured at the electrode surface. DNA was immobilized on gold by forming mixed monolayers of thiol-derivitized, single-stranded oligonucleotide and 6-mercapto-1-hexanol. The saturated amount of charge-compensating redox marker in the DNA monolayer, determined using chronocoulometry, is directly proportional to the number of phosphate residues and thereby the surface density of DNA. This method permits quantitative determination of both single- and double-stranded DNA at electrodes. Surface densities of single-stranded DNA were precisely varied in the range of (1−10) × 1012 molecules/cm2, as determined by the electrochemical method, using mixed monolayers. We measured the hybridization efficiency of immobilized single-stranded DNA to complementary strands as a function of the immobilized DNA surface density and found that it exhibits a maximum with increasing surface density.
Voltage-Gated Sodium Channel Nav1.7 Maintains the Membrane Potential and Regulates the Activation and Chemokine-Induced Migration of a Monocyte-Derived Dendritic Cell Subset (2011)

Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 ± 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets.
Human Glucagon Receptor Antagonists with Thiazole Cores. A Novel Series with Superior Pharmacokinetic Properties (2009)

The aim of the work presented here was to design and synthesize potent human glucagon receptor antagonists with improved pharmacokinetic (PK) properties for development of pharmaceuticals for the treatment of type 2 diabetes. We describe the preparation of compounds with cyclic cores (5-aminothiazoles), their binding affinities for the human glucagon and GIP receptors, as well as affinities for rat, mouse, pig, dog, and monkey glucagon receptors. Generally, the compounds had slightly less glucagon receptor affinity compared to compounds of the previous series, but this was compensated for by much improved PK profiles in both rats and dogs with high oral bioavailabilities and sustained high plasma exposures. The compounds generally showed species selectivity for glucagon receptor binding with poor affinities for the rat, mouse, rabbit, and pig receptors. However, dog and monkey glucagon receptor affinities seem to reflect the human situation. One compound of this series, 18, was tested intravenously in an anesthetized glucagon-challenged monkey model of hyperglucagonaemia and hyperglycaemia and was shown dose-dependently to decrease glycaemia. Further, high plasma exposures and a long plasma half-life (5.2 h) were obtained.
Improved Synthesis of N-Succinimidyl 4-[18F]Fluorobenzoate and Its Application to the Labeling of a Monoclonal Antibody Fragment (1994)

Our previously reported method for the 18F labeling of antibodies using N-succinimidyl 4-[18F]fluorobenzoate (SFB) involved a rather long synthesis time. Here we present an improved method for the synthesis of SFB which reduces the synthesis time by about 45 min. A reaction time of 5-8 min (versus 25 min for the original procedure) was sufficient in the fluorination step to form 4-[18F]fluorobenzaldehyde in high yield. In the original method, 30-35 min was necessary to convert 4-[18F]fluorobenzoic acid to SFB using dicyclohexylcarbodiimide and N-hydroxysuccinimide. When N,N'-disuccinimidyl carbonate was used, facile conversion of 4-fluorobenzoic acid to SFB was seen at a micromolar level. At a tracer level, no product was formed at room temperature; however, complete consumption of starting material was observed. Heating at 150 degrees C resulted in the formation of SFB in more than 80% yield in 1-3 min. HPLC purification of SFB was necessary since use of crude SFB, or SFB purified using a silica solid-phase cartridge column, resulted in lower protein coupling yields. Furthermore, use of crude SFB resulted in cross-linking and lower immunoreactivity of antibody. Largely as a result of the considerable reduction in total labeling time, these modifications have increased the amount of 18F-labeled antibody available per 100 mCi of [18F]fluoride by 30-35%.
Bicyclic Imides and Isoindolines1 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBicyclic Imides and Isoindolines1Charles H. Grogan and Leonard M. RiceCite this: J. Med. Chem. 1963, 6, 6, 802–805Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/jm00342a042https://doi.org/10.1021/jm00342a042research-articleACS PublicationsRequest reuse permissionsArticle Views178Altmetric-Citations6LEARN 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
Kallistatin: a novel human tissue kallikrein inhibitor. Purification, characterization, and reactive center sequence. (1992)

A novel human tissue kallikrein inhibitor designated as kallistatin has been purified from plasma to apparent homogeneity by polyethylene glycol fractionation and successive chromatography on heparin-Agarose, DEAE-Sepharose, hydroxylapatite, and phenyl-Superose columns. A purification factor of 4350 was achieved with a yield of approximately 1.35 mg per liter of plasma. The purified inhibitor migrates as a single band with an apparent molecular mass of 58 kDa when analyzed on SDS-polyacrylamide gel electrophoresis under reducing conditions. It is an acidic protein with pI values ranging from 4.6 to 5.2. No immunological cross-reactivity was found by Western blot analyses between kallistatin and other serpins. Kallistatin inhibits human tissue kallikrein's activity toward kininogen and tripeptide substrates. The second-order reaction rate constant (ka) was determined to be 2.6 x 10(4) M-1 s-1 using Pro-Phe-Arg-MCA. The inhibition is accompanied by formation of an equimolar, heat- and SDS-stable complex between tissue kallikrein and kallistatin, and by generation of a small carboxyl-terminal fragment from the inhibitor due to cleavage at the reactive site by tissue kallikrein. Heparin blocks kallistatin's complex formation with tissue kallikrein and abolishes its inhibitory effect on tissue kallikrein's activity. The amino-terminal residue of kallistatin is blocked. Sequence analysis of the carboxyl-terminal fragment generated from kallistatin reveals the reactive center sequence from P1' to P15', which shares sequence similarity with, but is different from known serpins including protein C inhibitor, alpha 1-antitrypsin, and alpha 1-antichymotrypsin. The results show that kallistatin is a new member of the serpin superfamily that inhibits human tissue kallikrein.
Cloning and Characterization of a Novel Avirulence Gene (arp3) fromXanthomonas oryzae pv. oryzae (2004)

A novel avirulence gene was cloned from Xanthomonas oryzae pv. oryzae strain PX0339, which is the standard representative of the Philippines race 9a. The full-length gene spans 2118 bp and encodes a protein of 705 amino acids. BLAST search in NCBI indicated that the gene belongs to avrBs3 gene family, and designated arp3 (AvrBs3-related protein 3, arp3). The central region of the arp3 contains only 5.5 copies of 102bp repeats, the smallest copy number of repeats found in avrBs3 gene family by now. Together with the repeats is heptad repeats, resembling leucine zippers. Three functional nuclear localization signals and an acidic activation domain are also found in the C-terminal region. However, the arp3 lacks of two segments in its N-terminal region, which is unique in avrBs3 gene family. Southern blotting data showed that the arp3 is present as a single-copy in genomic DNA of PX0339 and locus in plasmid clone. The arp3 could be expressed in vitro in Escherichia coli BL21 and a 128kDa fusion protein was detected by Western analysis.
A portable near infrared spectroscopy system for bedside monitoring of newborn brain (2005)

As a result, a shot-limited SNR of 67 dB has been achieved for 10 Hz temporal resolution. The system can operate more than 30 hours without recharging when an off-the-shelf 1850 mAh-7.2 V battery is used. Laboratory tests with optical phantoms and preliminary data recorded in NICU demonstrate the potential of the system as a reliable clinical tool to be employed in the bedside regional monitoring of newborn brain metabolism under intensive care.
American college of rheumatology preliminary definition of improvement in rheumatoid arthritis (1995)

We present a definition of improvement which we hope will be used widely in RA trials.
The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration (2007)

Endocannabinoids are released following brain injury and may protect against excitotoxic damage during the acute stage of injury. Brain injury also activates microglia in a secondary inflammatory phase of more widespread damage. Most drugs targeting the acute stage are not effective if administered more than 6 hours after injury. Therefore, drugs targeting microglia later in the neurodegenerative cascade are desirable. We have found that cannabinoid CB2 receptors are up-regulated during the activation of microglia following brain injury. Specifically, CB2-positive cells appear in the rat brain following both hypoxia-ischemia (HI) and middle cerebral artery occlusion (MCAO). This may regulate post-injury microglial activation and inflammatory functions. In this paper we review in vivo and in vitro studies of CB2 receptors in microglia, including our results on CB2 expression post-injury. Taken together, studies show that CB2 is up-regulated during a process in which microglia become primed to proliferate, and then become fully reactive. In addition, CB2 activation appears to prevent or decrease microglial activation. In a rodent model of Alzheimer's disease microglial activation was completely prevented by administration of a selective CB2 agonist. The presence of CB2 receptors in microglia in the human Alzheimer's diseased brain suggests that CB2 may provide a novel target for a range of neuropathologies. We conclude that the administration of CB2 agonists and antagonists may differentially alter microglia-dependent neuroinflammation. CB2 specific compounds have considerable therapeutic appeal over CB1 compounds, as the exclusive expression of CB2 on immune cells within the brain provides a highly specialised target, without the psychoactivity that plagues CB1 directed therapies.
Nonsense-Mediated mRNA Decay Effectors Are Essential for Zebrafish Embryonic Development and Survival (2009)

The nonsense-mediated mRNA decay (NMD) pathway promotes rapid degradation of mRNAs containing premature translation termination codons (PTCs or nonsense codons), preventing accumulation of potentially detrimental truncated proteins. In metazoa, seven genes (upf1, upf2, upf3, smg1, smg5, smg6, and smg7) have been identified as essential for NMD; here we show that the zebrafish genome encodes orthologs of upf1, upf2, smg1, and smg5 to smg7 and two upf3 paralogs. We also show that Upf1 is required for degradation of PTC-containing mRNAs in zebrafish embryos. Moreover, its depletion has a severe impact on embryonic development, early patterning, and viability. Similar phenotypes are observed in Upf2-, Smg5-, or Smg6-depleted embryos, suggesting that zebrafish embryogenesis requires an active NMD pathway. Using cultured cells, we demonstrate that the ability of a PTC to trigger NMD is strongly stimulated by downstream exon-exon boundaries. Thus, as in mammals and plants but in contrast to invertebrates and fungi, NMD is coupled to splicing in zebrafish. Our results together with previous studies show that NMD effectors are essential for vertebrate embryogenesis and suggest that the coupling of splicing and NMD has been maintained in vertebrates but lost in fungi and invertebrates.
3,5,3′‐triiodothyronine (T3) is a survival factor for pancreatic β‐cells undergoing apoptosis (2005)

3,5,3'-triiodothyronine (T3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T3 has largely been demonstrated and the pathways via which T3 promotes cell growth have been recently investigated. Type 1 diabetes (T1D) is due to the destruction of beta-cells, which occurs even through apoptosis. Aim of our study was to analyze whether T3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis. We have demonstrated that T3 promotes cell proliferation in islet beta-cell lines (rRINm5F and hCM) provoking an increment in cell number (up to 55%: rRINm5F and 45%: hCM), cell viability, and BrdU incorporation, and regulating the cell cycle-related molecules (cyc A, D1, E, and p27(kip1)). T3 inhibited the apoptotic process induced by streptozocin, S-Nitroso-N-Acetylpenicylamine (SNAP), and H2O2 via regulation of the pro- and anti-apoptotic factors Bcl-2, Bcl-XL, Bad, Bax, and Caspase 3. The T3 protective effect was PI-3 K-, but not MAPK- or PKA-mediated, involving pAktThr308. Thus, T3 could be considered a survival factor protecting islet beta-cells from apoptosis.
The hepoxilin analog PBT-3 induces apoptosis in BCR-ABL-positive K562 leukemia cells. (2004)

These results suggest that PBT analogs may provide a new platform for the development of apoptotic drugs in leukemia.
Characterization of an Extracellular -Amylase from Bacillus megaterium sensu stricto (1980)

Bacillus megaterium sensu stricto (NCIB 7581) produced amylase throughout exponential growth and during the early-stationary phase. Enzyme synthesis occurred in the absence of α-glucans but the yield was maximal when malt extract or starch was supplied as carbon source. Of the nitrogen sources examined, soya flour stimulated the highest yield of amylase. The enzyme was susceptible to reagents that react with thiol groups and had an exo-action on starch yielding maltose with a β-anomeric configuration. It is concluded that the principal starch-hydrolysing enzyme from B. megaterium NCIB 7581 is a (1→4)-α-d-glucan maltohydrolase similar in its properties to other Bacillus and plant β-amylases.
A Potent Small-Molecule Inhibitor of the MDM2–p53 Interaction (MI-888) Achieved Complete and Durable Tumor Regression in Mice (2013)

We previously reported the discovery of a class of spirooxindoles as potent and selective small-molecule inhibitors of the MDM2-p53 interaction (MDM2 inhibitors). We report herein our efforts to improve their pharmacokinetic properties and in vivo antitumor activity. Our efforts led to the identification of 9 (MI-888) as a potent MDM2 inhibitor (Ki = 0.44 nM) with a superior pharmacokinetic profile and enhanced in vivo efficacy. Compound 9 is capable of achieving rapid, complete, and durable tumor regression in two types of xenograft models of human cancer with oral administration and represents the most potent and efficacious MDM2 inhibitor reported to date.
Secure virtual private networks: the future of data communications (1999)

The Internet is an almost ideal means for information retrieval and exchange. It is cost-effective, easy to use and easily accessible. However, it can also be susceptible to devious practices such as data tempering, eavesdropping and theft. This paper analyses secure virtual private networks (VPNs) and their use in countering the problems of the Internet. Copyright © 1999 John Wiley & Sons, Ltd.
Carbon Nanotube Thin Film Coating for Improved Thermal Management in Piezoceramic Sheet Actuators (2006)

Minimally intrusive carbon nanotube coatings are used to demonstrate improved thermal management in piezoceramic actuators. Because of their nanoscale cylindrical structure, carbon nanotubes provide an order of magnitude increase in the exposed surface area compared to the uncoated piezoceramic sheet. This along with their excellent thermal conductivity allows the nanotube coating to act as a heat sink, drawing energy away from the bulk piezoceramic material and dissipating it to the atmosphere. Reduced self-heating of the actuator minimizes capacitive losses and reduces actuator power consumption. To demonstrate the concept, carbon nanotube films are deposited on the surfaces of 0.025 cm thick, commercially available PZT-5H sheets. Two types of carbon-based nanostructures are used to construct the coatings - (1) fluorine functionalized single-walled nanotubes (F-SWNTs) and (2) multiwalled nanotubes (MWNTs). The F-SWNT coating performs better than the MWNT coating and gives up to 40% reduction in surface temperature and 25% reduction in power consumption compared to the baseline uncoated actuator (for the same induced-strain level).
Purification and properties of a xylanase from Streptomyces lividans (1986)

An extracellular xylanase produced by a cellulase-negative mutant strain of Streptomyces lividans 1326 was purified to homogeneity. The purified enzyme has an apparent Mr of 43,000 and pI of 5.2. The pH and temperature optima for the activity were 6.0 and 60 degrees C respectively, and the Km and Vmax. values, determined with a soluble oat spelts xylan, were 0.78 mg/ml and 0.85 mmol/min per mg of enzyme. The xylanase showed no activity towards CM-cellulose and p-nitrophenyl beta-D-xyloside. The enzyme degraded xylan, producing mainly xylobiose, a mixture of xylo-oligosaccharides and a small amount of xylose as end products. Its pattern of action on beta-1,4-D-xylan indicates that it is a beta-1,4-endoxylanase (EC 3.2.1.8).