gebhart/patrepeval huggingface dataset:
SAR of Carbon‐Linked, 2‐Substituted Purines: Synthesis and Characterization of AP23451 as a novel Bone‐Targeted Inhibitor of Src Tyrosine Kinase With In Vivo Anti‐Resorptive Activity (2008)

Targeted disruption of the pp60(src) (Src) gene has implicated this tyrosine kinase in osteoclast-mediated bone resorption and as a therapeutic target for the treatment of osteoporosis and other bone-related diseases. Here, we describe structure activity relationships of a novel series of carbon-linked, 2-substituted purines that led to the identification of AP23451 as a potent inhibitor of Src tyrosine kinase with antiresorptive activity in vivo. AP23451 features the use of an arylphosphinylmethylphosphinic acid moiety which confers bone-targeting properties to the molecule, thereby increasing local concentrations of the inhibitor to actively resorbing osteoclasts at the bone interface. AP23451 exhibited an IC50 = 68 nm against Src kinase; an X-ray crystal structure of the molecule complexed with Src detailed the molecular interactions responsible for its Src inhibition. In vivo, AP23451 demonstrated a dose-dependent decrease in PTH-induced hypercalcemia. Moreover, AP23517, a structurally and biochemically similar molecule with comparable activity (IC50 = 73 nm) except devoid of the bone-targeting element, demonstrated significantly reduced in vivo efficacy, suggesting that Src activity was necessary but not sufficient for in vivo activity in this series of compounds.
The complete genome of hyperthermophile Methanopyrus kandleri AV19 and monophyly of archaeal methanogens (2002)

We have determined the complete 1,694,969-nt sequence of the GC-rich genome of Methanopyrus kandleri by using a whole direct genome sequencing approach. This approach is based on unlinking of genomic DNA with the ThermoFidelase version of M. kandleri topoisomerase V and cycle sequencing directed by 2'-modified oligonucleotides (Fimers). Sequencing redundancy (3.3x) was sufficient to assemble the genome with less than one error per 40 kb. Using a combination of sequence database searches and coding potential prediction, 1,692 protein-coding genes and 39 genes for structural RNAs were identified. M. kandleri proteins show an unusually high content of negatively charged amino acids, which might be an adaptation to the high intracellular salinity. Previous phylogenetic analysis of 16S RNA suggested that M. kandleri belonged to a very deep branch, close to the root of the archaeal tree. However, genome comparisons indicate that, in both trees constructed using concatenated alignments of ribosomal proteins and trees based on gene content, M. kandleri consistently groups with other archaeal methanogens. M. kandleri shares the set of genes implicated in methanogenesis and, in part, its operon organization with Methanococcus jannaschii and Methanothermobacter thermoautotrophicum. These findings indicate that archaeal methanogens are monophyletic. A distinctive feature of M. kandleri is the paucity of proteins involved in signaling and regulation of gene expression. Also, M. kandleri appears to have fewer genes acquired via lateral transfer than other archaea. These features might reflect the extreme habitat of this organism.
Association study of the 5‐HT6 receptor gene in schizophrenia (1999)

Serotonergic (5-hydroxytryptamine; 5-HT) transmission may play an important role in the treatment and/or pathogenesis of schizophrenia. Previous studies reported that several atypical antipsychotic agents have high affinities for the 5-HT6 receptor. The 5-HT6 receptor gene polymorphism might contribute to the genetic background of this disorder. One hundred and fifty unrelated patients with schizophrenia and 150 unrelated healthy controls were genotyped for a biallelic polymorphism (267C/T) at the 5-HT6 receptor gene. No significant positive association between the 5-HT6 receptor genotype and schizophrenia was observed. Our results suggests that the 267C/T polymorphism of the 5-HT6 receptor gene may not be involved in the susceptibility to schizophrenia. Am J. Med. Genet. (Neuropsychiatr. Genet.) 88:120–122, 1999. © 1999 Wiley-Liss, Inc.
On Baile's Strand (1993)

L'histoire de Cuchulain est la pièce dans la pièce, la tragédie du héros dans la comédie burlesque des personnages secondaires. L'Aveugle prépare le destin de Cuchulain et son imagination change en légende la réalité de l'action. Dans l'intrigue principale, le tournant du drame est le serment, thème introduit par l'Aveugle. La cérémonie du feu, le chant des femmes, le sacrifice du fils de Cuchulain et la propre lutte du héros contre les vagues suggèrent un rituel. Rituel et surnaturel contribuent à l'impression de fatalité. L'intrigue tragique reflète l'intrigue burlesque de sorte que les deux pièces ne constituent qu'un seul acte avec une structure en miroirs. L'Aveugle est l'anti-moi de Conchubar. Le Fou est l'exacte contrepartie de Cuchulain, une figure anti-héroïque. Le Fou et l'Aveugle peuvent être considérés comme symbolisant des principes qui opèrent dans l'esprit de Cuchulain. Le Fou est l'intuition et l'imagination, l'Aveugle l'intelligence pratique et la prudence. Cuchulain et Conchubar sont des figures complémentaires, un homme et son masque. Le conflit qui les oppose est une querelle entre deux aspects d'une même personnalité. Puisque le Fou et l'Aveugle sont deux principes de l'esprit de Cuchulain, que Cuchulain et Conchubar sont deux figures complémentaires, et qu'il y a correspondance entre les deux personnages secondaires et leurs homologues tragiques, les spectateurs ont l'impression que toute la pièce se passe dans l'esprit de Cuchulain.
Neural Correlates of Tasting Concentrated Quinine and Sugar Solutions (2002)

Behavioral, ethological, and electrophysiological evidence suggests that the highly unpleasant, bitter taste of a concentrated quinine hydrochloride (QHCL) should activate the human amygdala. In the present study, healthy subjects tasted 0.02 M QHCL or water while regional cerebral blood flow (rCBF) was assayed with H(2)(15)O PET. Subjects were also studied while tasting a pleasant sucrose solution and resting with eyes closed (ECR). Tasting QHCL significantly increased rCBF within the left amygdala relative to control conditions of tasting water and ECR. Sucrose and water caused small to moderate rCBF increases in the amygdala relative to ECR, but sucrose did not significantly increase activity within either amygdalae relative to water. In the frontal lobe, QHCL and sucrose both activated the right posterior orbitofrontal cortex (OFC) relative to water, but portions of the anterior OFC and inferior frontal pole showed valence specific responses to QHCL. These data indicate that the left amygdala responds robustly to QHCL and more moderately to nonaversive sapid stimuli, both pleasant and unpleasant gustatory stimuli activate the right posterior OFC, and the left inferior frontal pole/anterior OFC demonstrates valence-specific responses to aversive gustatory stimuli.
Genetic characterization of human immunodeficiency virus type 1 nef gene products translated in vitro and expressed in mammalian cells (1991)

Expression of the human immunodeficiency virus type 1 nef gene was studied by in vitro transcription-translation and by transfection into monkey COS cells. Two Nef-related peptides, of 27 and 25 kDa, were identified by immunoprecipitation with anti-Nef antibodies. The relation between these two proteins was determined by metabolically labeling transfected COS cells and by deleting the initiator methionine of nef. We found that the 25-kDa polypeptide is not a cleavage product of 27-kDa Nef but rather is initiated from an internal ATG 57 bases downstream from the Nef initiation site. Myristoylation of the 27-kDa but not of the 25-kDa Nef was demonstrated by the contranslational modification of Nef in an in vitro reticulocyte translation system. The myristoylation pattern of the two Nef polypeptides further implies that the 25-kDa polypeptide lacks the amino terminus of 27-kDa Nef. Cellular localization of the various forms of Nef was studied in transiently transfected COS cells. Myristoylation was found to be necessary for membrane association of Nef. Myristoylation-deficient 27-kDa Nef mutant and 25-kDa Nef were confined to the soluble cytoplasmic fraction of transfected cells, whereas part of the wild-type 27-kDa Nef was membrane attached.
Reconfigurable hardware solutions for the digital rights management of digital cinema (2004)

This paper presents a hardware implementation of a decoder for Digital Cinema images. This decoder enables us to deal with image size of 2K with 24 frames per second and 36 bits per pixels. It is the first implementation known nowadays that perfectly fits in one single Virtex-II® FPGA and includes AES decryption, JPEG 2000 decompression and fingerprinting blocks. This hardware offers therefore high-quality image processing as well as robust security.
Direct analysis of bacterial fatty acids by Curie-point pyrolysis tandem mass spectrometry (1990)

Although pyrolysis-mass spectrometry (Py-MS) has been used for bacterial taxonomy, many of the mass spectral peaks used for discrimination of organisms have not been correlated to known biomolecules. This work presents the discrimination of five bacterial species based on Py-MS patterns containing only peaks that can be correlated to fatty acids and fatty acid derivatives. These correlations were confirmed by pyrolysis-tandem mass spectrometry of authentic standards and the organisms. The pattern recognition procedures used gave better results when only the fatty acid peaks were used in the analysis than when full spectra were used.
Mining human antibody repertoires (2010)

Human monoclonal antibodies (mAbs) have become drugs of choice for the management of an increasing number of human diseases. Human antibody repertoires provide a rich source for human mAbs. Here we review the characteristics of natural and non-natural human antibody repertoires and their mining with non-combinatorial and combinatorial strategies. In particular, we discuss the selection of human mAbs from naïve, immune, transgenic, and synthetic human antibody repertoires using methods based on hybridoma technology, clonal expansion of peripheral B cells, single-cell PCR, phage display, yeast display, and mammalian cell display. Our reliance on different strategies is shifting as we gain experience and refine methods to the efficient generation of human mAbs with superior pharmacokinetic and pharmacodynamic properties.
The use of bacterial spore formers as probiotics: Table 1 (2004)

The field of probiosis has emerged as a new science with applications in farming and aqaculture as alternatives to antibiotics as well as prophylactics in humans. Probiotics are being developed commercially for both human use, primarily as novel foods or dietary supplements, and in animal feeds for the prevention of gastrointestinal infections, with extensive use in the poultry and aquaculture industries. The impending ban of antibiotics in animal feed, the current concern over the spread of antibiotic resistance genes, the failure to identify new antibiotics and the inherent problems with developing new vaccines make a compelling case for developing alternative prophylactics. Among the large number of probiotic products in use today are bacterial spore formers, mostly of the genus Bacillus. Used primarily in their spore form, these products have been shown to prevent gastrointestinal disorders and the diversity of species used and their applications are astonishing. Understanding the nature of this probiotic effect is complicated, not only because of the complexities of understanding the microbial interactions that occur within the gastrointestinal tract (GIT), but also because Bacillus species are considered allochthonous microorganisms. This review summarizes the commercial applications of Bacillus probiotics. A case will be made that many Bacillus species should not be considered allochthonous microorganisms but, instead, ones that have a bimodal life cycle of growth and sporulation in the environment as well as within the GIT. Specific mechanisms for how Bacillus species can inhibit gastrointestinal infections will be covered, including immunomodulation and the synthesis of antimicrobials. Finally, the safety and licensing issues that affect the use of Bacillus species for commercial development will be summarized, together with evidence showing the growing need to evaluate the safety of individual Bacillus strains as well as species on a case by case by basis.
A Global Authentication Service without Global Trust (1986)

This paper describes a design for an authentication service for a very large scale, very long lifetime, distributed system. The paper introduces a methodology for describing authentication protocols that makes explicit the trust relationships amongst the participants. The authentication protocol is based on the primitive notion of composition of secure channels. The authentication model offered provides for the authentication of "roles", where a principal might exercise differing roles at differing times, whilst having only a single "identity". Roles are suitable for inclusion in access control lists. The naming of a role implies what entities are being trusted to authenticate the role. We provide a UID scheme that gives clients control over the time at which a name gets bound to a principal, thus controlling the effects of mutability of the name space.
Effects of bioflavonoids on hepatic P450 activities (1995)

1. The effects of tangeretin, green tea flavonoids, and other flavonoids on 7-ethoxyresorufin-O-deethylase (EROD; 450 1A), 7-pentoxyresorufin-O-dealkylase (PROD; P450 2B), p-nitrophenol hydroxylase (PNPH, P450 2E1), and erythromycin-N-demethylase (ERDM; P450 3A) were examined in induced rat liver microsomes. EROD, PNPH, ERDM, and nifedipine oxidase (NIFO; P450 3A4) were examined in human liver microsomes. 2. All flavonoids tested inhibited EROD activity at higher concentrations in liver microsomes. Flavone and tangeretin were potent inhibitors of EROD, with IC50's of 0.7 and 0.8 microM respectively in rat liver microsomes and 0.15 and 16 microM respectively in human liver microsomes. The green tea flavonoid (-)-epicatechin-3-gallate (ECG) was the most potent inhibitor of EROD in human liver microsomes (IC50 = 75 microM). The effect of the green tea flavonoids on EROD was complex; in addition to inhibition at high concentrations of flavonoid, moderate activation was seen at lower concentrations. 3. 450 2B-, 2E1- and 3A-dependent activities in rat and human liver microsomes were only moderately inhibited by any of the flavonoids tested, and, in general, ECG was the most potent inhibitor for these activities with IC50's ranging from 75 to 300 microM. 4. Tangeretin inhibited EROD activity (P450 1A2) in human liver microsomes in a competitive manner with a Ki = 68 nM. Tangeretin inhibited NIFO activity (P450 3A4) in human liver microsomes in an uncompetitive manner with Ki = 72 microM.
Techno-economic Analysis of Metal–Organic Frameworks for Hydrogen and Natural Gas Storage (2017)

A techno-economic analysis was conducted for metal–organic framework (MOF) adsorbents, which are promising candidates for light-duty vehicle on-board natural gas and hydrogen storage. The goal of this analysis was to understand cost drivers for large-scale (2.5 Mkg/year) MOF synthesis and to identify potential pathways to achieving a production cost of less than $10/(kg of MOF). Four MOFs were analyzed with four different metal centers and three different linkers: Ni2(dobdc) (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate; Ni-MOF-74), Mg2(dobdc) (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate; Mg-MOF-74), Zn4O(bdc)3 (bdc2– = 1,4-benzenedicarboxylate; MOF-5), and Cu3(btc)2 (btc3– = 1,3,5-benzenetricarboxylate; HKUST-1). Baseline costs are projected to range from $35/kg to $71/kg predicated on organic solvent (solvothermal) syntheses using an engineering scale-up of laboratory-demonstrated synthesis procedures and conditions. Two alternative processes were analyzed to evaluate the cost impact of reducing solvent usage: liquid assisted grinding (LAG) and aqueous synthesis. Cost projections from these alternative synthesis approaches range from $13/kg to $36/kg (representing 34–83% reductions), demonstrating the large impact of solvent on the baseline analysis. Finally, sensitivity studies were conducted to identify additional opportunities for achieving MOF production costs of less than $10/kg.
Identification of an Arabidopsis Feruloyl-Coenzyme A Transferase Required for Suberin Synthesis (2009)

All plants produce suberin, a lipophilic barrier of the cell wall that controls water and solute fluxes and restricts pathogen infection. It is often described as a heteropolymer comprised of polyaliphatic and polyaromatic domains. Major monomers include omega-hydroxy and alpha,omega-dicarboxylic fatty acids, glycerol, and ferulate. No genes have yet been identified for the aromatic suberin pathway. Here we demonstrate that Arabidopsis (Arabidopsis thaliana) gene AT5G41040, a member of the BAHD family of acyltransferases, is essential for incorporation of ferulate into suberin. In Arabidopsis plants transformed with the AT5G41040 promoter:YFP fusion, reporter expression is localized to cell layers undergoing suberization. Knockout mutants of AT5G41040 show almost complete elimination of suberin-associated ester-linked ferulate. However, the classic lamellar structure of suberin in root periderm of at5g41040 is not disrupted. The reduction in ferulate in at5g41040-knockout seeds is associated with an approximate stoichiometric decrease in aliphatic monomers containing omega-hydroxyl groups. Recombinant AT5G41040p catalyzed acyl transfer from feruloyl-coenzyme A to omega-hydroxyfatty acids and fatty alcohols, demonstrating that the gene encodes a feruloyl transferase. CYP86B1, a cytochrome P450 monooxygenase gene whose transcript levels correlate with AT5G41040 expression, was also investigated. Knockouts and overexpression confirmed CYP86B1 as an oxidase required for the biosynthesis of very-long-chain saturated alpha,omega-bifunctional aliphatic monomers in suberin. The seed suberin composition of cyp86b1 knockout was surprisingly dominated by unsubstituted fatty acids that are incapable of polymeric linkages. Together, these results challenge our current view of suberin structure by questioning both the function of ester-linked ferulate as an essential component and the existence of an extended aliphatic polyester.
Ultraviolet dispersion of the donor–acceptor charge transfer contribution to the second order hyperpolarizability (1978)

We have measured for the first time electric field induced optical mixing (ω+2ω=3ω) in the liquid state. Two molecules DANS (trans-4-dimethylamino-4′-nitrostilbene) and p-NA (p-nitroaniline) possessing large intramolecular charge transfer interactions were used and the second order mixing hyperpolariabilities β (3ω) were determined to be β (3ω) = (−7.2±2.6i) ×10−28 and β (3ω) = (+9.6±38i) ×10−30 esu for DANS and p-NA, respectively, with 3ω=3.50 eV. Combining these measurements with the simple two level quantum mechanical model yields the theoretical prediction of β (2ω) = (+38+15i) ×10−28 and β (2ω) = (+48+5.3i) ×10−30 esu for the second harmonic hyperpolarizability of DANS and p-NA, respectively. These predictions are not in good agreement with the experimental values ‖β (2ω) ‖ =2.1×10−28 esu (obtained using the measurements of Oudar and Chemla) and β (2ω) =+22×10−30 esu.
MicroPET: a high resolution PET scanner for imaging small animals (1997)

MicroPET is a high resolution positron emission tomography (PET) scanner designed for imaging small laboratory animals. It consists of a ring of 30 position-sensitive scintillation detectors, each with an 8/spl times/8 array of small lutetium oxyorthosilicate (LSO) crystals coupled via optical fibers to a multi-channel photomultiplier tube. The detectors have an intrinsic resolution averaging 1.68 mm, an energy resolution between 15 and 25% and 2.4 ns timing resolution at 511 keV. The detector ring diameter of microPET is 17.2 cm with an imaging field of view of 112 mm transaxially by 18 mm axially. The scanner has no septa and operates exclusively in 3D mode. Reconstructed image resolution 1 cm from the center of the scanner is 2.0 mm and virtually isotropic, yielding a volume resolution of 8 mm/sup 3/. For comparison, the volume resolution of state-of-the-art clinical PET systems is in the range of 50-75 mm/sup 3/. Initial images of phantoms have been acquired and are reported. A computer controlled bed is under construction and will incorporate a small wobble motion to improve spatial sampling. This is projected to further enhance spatial resolution. MicroPET is the first PET scanner to incorporate the new scintillator LSO and to our knowledge is the highest resolution multi-ring PET scanner currently in existence.
Effects of low-energy (1–1.5 kV) nitrogen-ion bombardment on sharply pointed tips: Sputtering, implantation, and metal-nitride formation (1997)

Low-energy (1–1.5 kV) nitrogen-ion bombardment of sharply pointed Fe-3 at. % Mo tips is performed, at room temperature and 473 K, by applying a negative voltage to the tip in the presence of nitrogen gas (10−3–10−5 Torr) in an ultrahigh vacuum atom-probe field-ion microscope (APFIM). Tip sharpening, as a consequence of sputtering, is observed directly in situ via APFIM. This sharpening phenomenon can be explained by the inertia effect on the trajectories of the field-emitted electrons and nitrogen ions that results in sputtering of the shank of the tip. We also observe that the implanted low-energy (1–1.5 kV) nitrogen ions react with the molybdenum atoms in solid solution in this Fe(Mo) alloy to produce immobile molecular diameter nitrides at room temperature and 473 K. The measured range profile of the implanted 1.5 kV nitrogen species is compared with results calculated using the TRIM.SP Monte Carlo code. This comparison implies that the ionized nitrogen molecules (N21+), generated by the field-emitted electrons, obtain the full potential energy of the tip before bombarding the tip’s surface and then dissociating into nitrogen ions (N1+) at or near the surface. The experimental nitrogen range profile is quantitatively fitted to the Edgeworth expansion of the normal distribution function.
Noninvasive Quantitative Imaging of Lymph Function in Mice (2007)

Our study demonstrates the ability to noninvasively and quantitatively image propulsive lymph flow, which could provide a new method to investigate lymph function and its change in response to potential therapeutics.
Cytokines in combination to treat radiation-induced myelosuppresssion: evaluation of SCF + glycosylated EPO + pegylated G-CSF as an emergency treatment in highly irradiated monkeys (2008)

Multicytokine therapy may be useful to counteract radiation-induced myelosuppression. We assessed the stem cell factor + glycosylated erythropoietin + pegylated granulocyte colony-stimulating factor combination (SEG) as an emergency treatment. SEG in highly irradiated monkeys efficacy appeared to be restricted to granulopoiesis. Early administration of Erythropoietin did not prevent radiation-induced anemia.