gebhart/patrepeval huggingface dataset:
Small-angle X-ray scattering-derived structure of the HIV-1 5′ UTR reveals 3D tRNA mimicry (2014)

The most conserved region of the HIV type 1 (HIV-1) genome, the ∼335-nt 5' UTR, is characterized by functional stem loop domains responsible for regulating the viral life cycle. Despite the indispensable nature of this region of the genome in HIV-1 replication, 3D structures of multihairpin domains of the 5' UTR remain unknown. Using small-angle X-ray scattering and molecular dynamics simulations, we generated structural models of the transactivation (TAR)/polyadenylation (polyA), primer-binding site (PBS), and Psi-packaging domains. TAR and polyA form extended, coaxially stacked hairpins, consistent with their high stability and contribution to the pausing of reverse transcription. The Psi domain is extended, with each stem loop exposed for interactions with binding partners. The PBS domain adopts a bent conformation resembling the shape of a tRNA in apo and primer-annealed states. These results provide a structural basis for understanding several key molecular mechanisms underlying HIV-1 replication.
PANS: a portable navigation platform (2002)

Research into self driving vehicles and driver monitoring systems has reached the point where long duration and distance field testing has become feasible. However, vehicle and computer systems which provide the functionality to accomplish these tests have been too expensive or inconvenient. This paper describes a simple, yet powerful platform, designed to work on any passenger vehicle, developed at Carnegie Mellon University. The platform, called PANS (Portable Advanced Navigation Support), has allowed researchers at Carnegie Mellon University to log over 6000 autonomous steering miles in the last 6 months.
INTEGRATED MEMS SWITCH TECHNOLOGY ON SOI-CMOS (2008)

We describe an RF MEMS contact switch technology that has been integrated above a 0.5um silicon RFCMOS-on-SOI process. This integration strategy combines a MEMS gold cantilever contact-switch with a custom silicon-on-insulator IC platform. This IC platform provides several power management functions critical for MEMS including high voltage generation, control and analog/digital/RF circuits... The technology also includes a waferlevel-package dielectric encapsulation process for the MEMS device which is hermetic and compatible with low cost packaging processes.
Die Fluoreszenz- und Phosphoreszenzspektren der Phenanthroline (1968)

Mit Hilfe der Fluoreszenz-, Fluoreszenzanregungs- und Phosphoreszenzspektren sowie der APF-, APPh-, FP- und PhP-Spektren wurde eine Zuordnung der Elektronenübergänge für die 10 isomeren Phenanthroline vorgenommen. Dabei zeigte sich wie in vorhergehenden Arbeiten, daß für die spektroskopischen Eigenschaften nicht die Symmetrie der Verbindungen, sondern nur die gegenseitige Stellung der beiden N-Atome in den äußeren Ringen entscheidend ist. Die Schwingungsübergänge für den Grund- und Anregungszustand werden diskutiert.
Structural determinants for the interaction of lipopolysaccharide binding protein with purified high density lipoproteins: role of apolipoprotein A-I (1997)

The interaction of lipopolysaccharide binding protein (LBP) with apolipoprotein (apo)A-I on high density lipoproteins (HDL) was studied in solid phase ligand binding assays with a biotinylated LBP-specific antibody. The association was dependent on LBP concentration and enhanced in the presence of lipopolysaccharide (LPS). Maximal enhancement was measured at an LPS/LBP molar ratio of 6. To identify regions on apoA-I that participate directly or indirectly in the interaction between LBP and HDL, we attempted to inhibit LBP association with a panel of mapped apoA-I-specific monoclonal antibodies. Whereas some antibodies were effective inhibitors, others were not, even though they bound apoA-I. Furthermore, selected apoA-I synthetic peptides inhibited the antibody-mediated interference of the HDL/LBP interaction. Although no specific mechanism can be defined for the basis of the inhibitory effects of the antibodies on the association of LBP with HDL, we identified a role for three unique regions on apoA-I between residues 1-31, 95-164, and 178-200. These results suggested that apoA-I is a key component in the association of LBP with HDL and may play an important role in the biologic activity of LPS/LBP complexes.
Selective inhibitors of cytosolic or secretory phospholipase A2 block TNF-induced activation of transcription factor nuclear factor-kappa B and expression of ICAM-1. (1998)

TNF signaling mechanisms involved in activation of transcription factor NF-kappaB were studied in the human keratinocyte cell line HaCaT. We show that TNF-induced activation of NF-kappaB was inhibited by the well-known selective inhibitors of cytosolic phospholipase A2 (cPLA2): the trifluoromethyl ketone analogue of arachidonic acid (AACOCF3) and methyl arachidonyl fluorophosphate. The trifluoromethyl ketone analogue of eicosapentaenoic acid (EPACOCF3) also suppressed TNF-induced NF-kappaB activation and inhibited in vitro cPLA2 enzyme activity with a similar potency as AACOCF3. The arachidonyl methyl ketone analogue (AACOCH3) and the eicosapentanoyl analogue (EPACHOHCF3), which both failed to inhibit cPLA2 enzyme activity in vitro, had no effect on TNF-induced NF-kappaB activation. TNF-induced NF-kappaB activation was also strongly reduced in cells stimulated in the presence of the secretory PLA2 (sPLA2) inhibitors 12-epi-scalaradial and LY311727. Addition of excess arachidonic acid suppressed the inhibitory effect of 12-epi-scalaradial and LY311727. Moreover, both methyl arachidonyl fluorophosphate and 12-epi-scalaradial blocked TNF-mediated enhancement of expression of ICAM-1. Activation of NF-kappaB by IL-1beta was markedly less sensitive to both cPLA2 and sPLA2 inhibitors. The results indicate that both cPLA2 and sPLA2 may be involved in the TNF signal transduction pathway leading to nuclear translocation of NF-kappaB and to NF-kappaB-activated gene expression in HaCaT cells.
cDNA cloning of granzyme C, a granule-associated serine protease of cytolytic T lymphocytes. (1988)

A cDNA clone corresponding to the complete amino acid sequence of a putative protease CCP2 of murine cytotoxic T lymphocytes was isolated and sequenced. The clone encodes a 248-residue long serine esterase. The deduced N-terminal amino acid sequence is identical over 40 residues to that of granzyme C, a protease of unknown function present in granules of cytotoxic lymphocytes. Analysis of the sequence of granzyme C/CCP2 reveals high homology to other granzyme proteases, i.e. granzyme A (40%) and granzyme B (67%) and to rat mast cell protease II (46%). The amino acids lining the specificity pocket are well conserved between granzyme B, C, and rat mast cell protease II, but not granzyme A, suggesting a similar general specificity of these three proteases.
27-Hydroxycholesterol Is an Endogenous Ligand for Liver X Receptor in Cholesterol-loaded Cells (2001)

The nuclear receptors liver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta (NR1H2) are important regulators of genes involved in lipid metabolism, including ABCA1, ABCG1, and sterol regulatory element-binding protein-1c (SREBP-1c). Although it has been demonstrated that oxysterols are LXR ligands, little is known about the identity of the physiological activators of these receptors. Here we confirm earlier studies demonstrating a dose-dependent induction of ABCA1 and ABCG1 in human monocyte-derived macrophages by cholesterol loading. In addition, we show that formation of 27-hydroxycholesterol and cholestenoic acid, products of CYP27 action on cholesterol, is dependent on the dose of cholesterol used to load the cells. Other proposed LXR ligands, including 20(S)-hydroxycholesterol, 22(R)-hydroxycholesterol, and 24(S),25-epoxycholesterol, could not be detected under these conditions. A role for CYP27 in regulation of cholesterol-induced genes was demonstrated by the following findings. 1) Introduction of CYP27 into HEK-293 cells conferred an induction of ABCG1 and SREBP-1c; 2) upon cholesterol loading, CYP27-expressing cells induce these genes to a greater extent than in control cells; 3) in CYP27-deficient human skin fibroblasts, the induction of ABCA1 in response to cholesterol loading was ablated; and 4) in a coactivator association assay, 27-hydroxycholesterol functionally activated LXR. We conclude that 27-hydroxylation of cholesterol is an important pathway for LXR activation in response to cholesterol overload.
How theories evolved concerning the mechanism of action of barbiturates (2012)

The barbiturate phenobarbital has been in use in the treatment of epilepsy for 100 years. It has long been recognized that barbiturates act by prolonging and potentiating the action of γ-aminobutyric acid (GABA) on GABA(A) receptors and at higher concentrations directly activating the receptors. A large body of data supports the concept that GABA(A) receptors are the primary central nervous system target for barbiturates, including the finding that transgenic mice with a point mutation in the β3 GABA(A) -receptor subunit exhibit diminished sensitivity to the sedative and immobilizing actions of the anesthetic barbiturate pentobarbital. Although phenobarbital is only modestly less potent as a GABA(A) -receptor modulator than pentobarbital, phenobarbital is minimally sedating at effective anticonvulsant doses. Possible explanations for the reduced sedative effect of phenobarbital include more regionally restricted action; partial agonist activity; reduced propensity to directly activate GABA(A) receptors (possibly including extrasynaptic receptors containing δ subunits); and reduced activity at other ion channel targets, including voltage-gated calcium channels. In recent years, substantial progress has been made in defining the structural features of GABA(A) receptors responsible for gating and allosteric modulation by drugs. Although the precise sites of action of barbiturates have not yet been defined, the second and third transmembrane domains of the β subunit appear to be critical; binding may involve a pocket formed by β-subunit methionine 286 as well as α-subunit methionine 236. In addition to effects on GABA(A) receptors, barbiturates block AMPA/kainate receptors, and they inhibit glutamate release through an effect on P/Q-type high-voltage activated calcium channels. The combination of these various actions likely accounts for their diverse clinical activities. Despite the remarkable progress of the last century, there is still much to learn about the actions of barbiturates that can be applied to the discovery of new, more therapeutically useful agents.
Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays (1999)

Two strategies are described for detecting constitutive or induced protein-protein interactions in intact mammalian cells; these strategies are based on oligomerization domain-assisted complementation of rationally designed fragments of the murine enzyme dihydrofolate reductase (DHFR; EC 1.5.1.3). We describe a dominant clonal-selection assay of stably transfected cells expressing partner proteins FKBP (FK506 binding protein) and FRAP (FKBP-rapamycin binding protein) fused to DHFR fragments and show a rapamycin dose-dependent survival of clones that requires approximately 25 molecules of reconstituted DHFR per cell. A fluorescence assay also is described, based on stoichiometric binding of fluorescein-methotrexate to reconstituted DHFR in vivo. Formation of the FKBP-rapamycin-FRAP complex is detected in stably and transiently transfected cells. Quantitative rapamycin dose-dependence of this complex is shown to be consistent with in vitro binding and distinguishable from a known constitutive interaction of FKBP and FRAP. We also show that this strategy can be applied to study membrane protein receptors, demonstrating dose-dependent activation of the erythropoietin receptor by ligands. The combination of these clonal-selection and fluorescence assays in intact mammalian cells makes possible selection by simple survival, flow cytometry, or both. High-throughput drug screening and quantitative analysis of induction or disruption of protein-protein interactions are also made possible.
Hyperstability and Substrate Promiscuity in Laboratory Resurrections of Precambrian β-Lactamases (2013)

We report a sequence reconstruction analysis targeting several Precambrian nodes in the evolution of class-A β-lactamases and the preparation and experimental characterization of their encoded proteins. Despite extensive sequence differences with the modern enzymes (~100 amino acid differences), the proteins resurrected in the laboratory properly fold into the canonical lactamase structure. The encoded proteins from 2-3 billion years (Gyr)-old β-lactamase sequences undergo cooperative two-state thermal denaturation and display very large denaturation temperature enhancements (~35 °C) relative to modern β-lactamases. They degrade different antibiotics in vitro with catalytic efficiencies comparable to that of an average modern enzyme. This enhanced substrate promiscuity is not accompanied by significant changes in the active-site region as seen in static X-ray structures, suggesting a plausible role for dynamics in the evolution of function in these proteins. Laboratory resurrections of 2-3 Gyr-old β-lactamases also endowed modern microorganisms with significant levels of resistance toward a variety of antibiotics, opening up the possibility of performing laboratory replays of the molecular tape of lactamase evolution. Overall, these results support the notions that Precambrian life was thermophilic and that proteins can evolve from substrate-promiscuous generalists into specialists during the course of natural evolution. They also highlight the biotechnological potential of laboratory resurrection of Precambrian proteins, as both high stability and enhanced promiscuity (likely contributors to high evolvability) are advantageous features in protein scaffolds for molecular design and laboratory evolution.
Some taste substances are direct activators of G-proteins (1994)

Amphiphilic substances may stimulate cellular events through direct activation of G-proteins. The present experiments indicate that several amphiphilic sweeteners and the bitter tastant, quinine, activate transducin and Gi/Go-proteins. Concentrations of taste substances required to activate G-proteins in vitro correlated with those used to elicit taste. These data support the hypothesis that amphiphilic taste substances may elicit taste through direct activation of G-proteins.
Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma (2006)

Allergic asthma is associated with airway epithelial cell mucous metaplasia and mucin hypersecretion, but the consequences of mucin hypersecretion on airway function are unclear. Recently, a peptide derived from the myristoylated alanine-rich C kinase substrate protein NH(2)-terminal sequence (MANS) was shown to inhibit methacholine (MCh)-induced mucin secretion from airway mucous cells by >90%. We studied the effect of intranasal pretreatment with this peptide on specific airway conductance (sGaw) during challenge with MCh in mice with allergen-induced mucous cell metaplasia. sGaw was noninvasively measured in spontaneously breathing restrained mice, using a double-chamber plethysmograph. Pretreatment with MANS peptide, but not a control peptide [random NH(2)-terminal sequence (RNS)], resulted in partial inhibition of the fall in sGaw induced by 60 mM MCh (mean +/- SE; baseline 1.15 +/- 0.06; MANS/MCh 0.82 +/- 0.05; RNS/MCh 0.55 +/- 0.05 cmH(2)O/s). The protective effect of MANS was also seen in mice challenged with allergen for 3 consecutive days to increase airway hyperresponsiveness, although the degree of protection was less (baseline 1.1 +/- 0.08; MANS/MCh, 0.65 +/- 0.06; RNS/MCh 0.47 +/- 0.03 cmH(2)O/s). Because routine sGaw measurement in mice includes nasal airways, the effectiveness of MANS was also confirmed in mice breathing through their mouths after nasal occlusion (baseline 0.92 +/- 0.05; MANS/MCh 0.83 +/- 0.06; RNS/MCh 0.61 +/- 0.03 cmH(2)O/s). In all instances, sGaw in the MANS-pretreated group was approximately 35% higher than in RNS-treated controls, and mucous obstruction accounted for approximately 50% of the MCh-induced fall in sGaw. In summary, mucin secretion has a significant role in airway obstruction in a mouse model of allergic asthma, and strategies to inhibit mucin secretion merit further investigation.
Potential sweetening agents of plant origin. Part 27. Stimulation of the gerbil's gustatory receptors by some potently sweet terpenoids (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPotential sweetening agents of plant origin. Part 27. Stimulation of the gerbil's gustatory receptors by some potently sweet terpenoidsEnrique. Vasquez, William. Jakinovich, N. P. Dhammika. Nanayakkara, Raouf A. Hussain, Myung Sook. Chung, and A. Douglas. KinghornCite this: J. Agric. Food Chem. 1993, 41, 8, 1305–1310Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://pubs.acs.org/doi/10.1021/jf00032a027https://doi.org/10.1021/jf00032a027research-articleACS PublicationsRequest reuse permissionsArticle Views197Altmetric-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
Brassinolide Application Improves the Drought Tolerance in Maize Through Modulation of Enzymatic Antioxidants and Leaf Gas Exchange (2011)

Brassinolides (BRs) are naturally occurring substances, which modulate plant growth and development events and have been known to improve the crop tolerance to abiotic stresses. In this study, possible role of exogenously applied brassinolide (BR) in alleviating the detrimental effects of drought in maize was evaluated in a rain-protected wire-house. Maize was subjected to drought at the start of tasseling for 6 days by withholding water application followed by foliar spray of BR (0.1 mg l−1) to assess the changes in growth, gas exchange, chlorophyll contents, protein, relative leaf water contents (RLWC), proline, malonialdehyde (MDA) and enzymatic antioxidants. Drought substantially reduced the maize growth in terms of plant height, leaf area and plant biomass. Moreover, substantial decrease in gas exchange attributes (net photosynthetic rate (A), transpiration rate (E), stomatal conductance (gs), water use efficiency (WUE), instantaneous water use efficiency (WUEi) and intercellular CO2 (Ci) was also recorded. However, exogenous application of BR remarkably improved the gas exchange attributes, plant height, leaf area, cobs per plant, seedling dry weight both under drought and well-watered conditions. BR-induced promotion in growth and physiological and metabolic activities were mediated through increased protein synthesis enabling maintenance of tissue water potential and activities of antioxidant enzymes lowering the lipid peroxidation under drought.
CD44 expression and regulation during mammary gland development and function (2000)

ABSTRACT The CD44v6 epitope has been widely reported to be expressed in human mammary carcinomas, yet its prognostic significance is controversial and its function in mammary tumors and mammary glands is unknown. To begin to resolve these issues, we analysed in detail the normal postnatal expression patterns and regulation of the CD44v6 epitope in murine mammary glands. We demonstrate that significant CD44v6 epitope expression is first seen during puberty, and that after puberty CD44v6 epitope expression follows the estrous cycle. CD44v6 epitope expression is observed in the myoepithelium and also less widely in luminal epithelial cells. During lactation, CD44v6 epitope expression is turned off and reappears during involution. The CD44 variant isoform bearing the v6 epitope is CD44v1-v10. Using HC11, a mammary epithelial cell line with stem cell characteristics, and facilitated by the cloning of the murine CD44 promoter, we show that growth factors and hormones which regulate ductal growth and differentiation modulate CD44 transcription. Together our data suggest that the CD44v6 epitope is expressed in mammary epithelial stems cells and in lineages derived from these cells, and that CD44v6 expression is regulated in part by hormones and growth factors such as IGF-1 and EGF which regulate the growth and differentiation of the mammary epithelium. The function of these same growth factors and hormones is often perturbed in mammary carcinomas, and we suggest that CD44v6 expression in tumors reflects this perturbation. We conclude that the expression of the CD44v6 epitope observed in some mammary tumors reflects the stem cell origin of breast tumors, and that whether or not the CD44v6 epitope is expressed in a mammary tumor is determined by the differentiation status of the tumor cells.
Extraocular retinoblastoma: A 13‐year experience (2003)

In the current study, the addition of ifosfamide and etoposide to a treatment regimen comprised of cisplatin, teniposide, vincristine, doxorubicin, and cyclophosphamide did not appear to improve the survival of patients with extraocular retinoblastoma. Patients with dissemination to the central nervous system or metastatic disease remain incurable and die of progressive disease, despite the aggressive treatment. A multicenter trial should be considered to evaluate the best strategy for these situations.
In Situ Optical Microscopy Investigations of Lithium and Sodium Film Formation in Buffered Room Temperature Molten Salts (1996)

Previous work performed in both sodium and lithium buffered chloroaluminate molten salts have shown that the addition of small amounts of promotes the reversible stripping behavior of lithium and sodium metal with cycling efficiencies between 80 and 90%. We have performed a series of optical studies in conjunction with electrochemical experiments at varying concentrations in both lithium and sodium chloride buffered melts. On investigation, the lithium deposit is dendritic in nature and does not form a uniform film on the tungsten electrode. After discharging at moderate current densities, disconnected lithium metal is observed at the electrode surface. In contrast, the sodium deposits as a uniform, flat film on the tungsten electrode with little or no dendritic growth. The sodium electrodeposits undergo complete stripping from the tungsten electrode without dendritic or disconnected sodium metal left on the electrode surface.