gebhart/patrepeval huggingface dataset:
Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. (1982)

Tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) directly activate in vitro Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), which normally requires unsaturated diacylglycerol. Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid. Under physiological conditions, the activation of this enzyme appears to be linked to the receptor-mediated phosphatidylinositol breakdown which may be provoked by a wide variety of extracellular messengers, eventually leading to the activation of specific cellular functions or proliferation. Using human platelets as a model system, TPA is shown to enhance the protein kinase C-specific phosphorylation associated with the release reaction in the total absence of phosphatidylinositol breakdown. Various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.
Structure–Activity Relationship Studies of a Macrocyclic AGRP-Mimetic Scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro] Yield Potent and Selective Melanocortin-4 Receptor Antagonists and Melanocortin-5 Receptor Inverse Agonists That Increase Food Intake in Mice (2018)

The melanocortin system has five receptors, and antagonists of the central melanocortin receptors (MC3R, MC4R) are postulated to be viable therapeutics for disorders of negative energy balance such as anorexia, cachexia, and failure to thrive. Agouti-related protein (AGRP) is an antagonist of the MC3R and an antagonist/inverse agonist of the MC4R. Biophysical NMR-based structural studies have demonstrated that the active sequence of this hormone, Arg-Phe-Phe, is located on an exposed β-hairpin loop. It has previously been demonstrated that the macrocyclic octapeptide scaffold c[Pro<sup>1</sup>-Arg<sup>2</sup>-Phe<sup>3</sup>-Phe<sup>4</sup>-Asn<sup>5</sup>-Ala<sup>6</sup>-Phe<sup>7</sup>-DPro<sup>8</sup>] is 16-fold less potent than AGRP at the mouse MC4R (mMC4R). Herein it was hypothesized that the Phe<sup>7</sup> position may be substituted to produce more potent and/or selective melanocortin receptor antagonist ligands based on this template. A 10-membered library was synthesized that substituted small (Gly), polar (Ser), acidic (Asp), basic (Lys), aliphatic (Leu, Nle, and Cha), and aromatic (Trp, Tyr, hPhe) amino acids to explore potential modifications at the Phe<sup>7</sup> position. The most potent mMC4R antagonist contained a Nle<sup>7</sup> substitution, was equipotent to the lead ligand 200-fold selective for the mMC4R over the mMC3R, and caused a significant increase in food intake when injected intrathecally into male mice. Three compounds possessed sigmoidal dose-response inverse agonist curves at the mMC5R, while the remaining seven decreased cAMP production from basal levels at a concentration of 100 μM. These findings will add to the knowledge base toward the development of potent and selective probes to study the role of the melanocortin system in diseases of negative energy balance and can be useful in the design of molecular probes to examine the physiological functions of the mMC5R.
Chaos applied to fluid mixing (1995)

Chaotic advection in perspective, H. Aref invariant manifold templates for chaotic advection, D. Beigie et al quantification of mixing in aperiodic chaotic flows, M. Liu et al Hamiltonian formulation of the equations of streamlines in three-dimensional steady flows, K. Bajer orientation dynamics and stretching of particles in unsteady, three-dimensional fluid flows - unsteady attractors, A.J. Szeri and L.G. Leal interaction of chaotic advection and diffusion, S.W. Jones resonant and chaotic advection in a curved pipe, P.E. Hydon application of chaotic advection to heat transfer, Hsueh-Chia Chang and M. Sen interacting two-dimensional vortex structures - point vortices, contour kinematics and stirring-properties, V.V. Meleshko and G.J.F. van Heijst an analytical study of chaotic stirring in tidal areas, S.P. Beerens et al stretching and alignment in chaotic and turbulent flows, M. Tabor and I. Klapper comparisons of mixing in chaotic and turbulent flows, K.B. Southerland et al tracer microstructure in the large-eddy dominated regime, R.T. Pierrehumbert spectra of local and nonlocal two-dimensional turbulence, R.T. Pierrehumbert et al.
Automatic spatial frequency selection algorithm for pattern recognition by correlation (1993)

We describe an approach to compute filters that automatically performs a spatial frequency selection to improve interclass discrimination and to reduce intraclass sensitivity. This approach is achieved by using as input to the filter synthesis a set of reference images to compute the filters and a set of distorted images to introduce the distortion or noise model of the reference images. Simulation results of correlation examples are provided for two pattern-recognition problems and are compared with the ones obtained with the standard minimum average correlation energy filters.
Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death (2006)

Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation. How PARP-1 activation leads to AIF release is not known. Here we identify PAR polymer as a cell death signal that induces release of AIF. PAR polymer induces mitochondrial AIF release and translocation to the nucleus. PAR glycohydrolase, which degrades PAR polymer, prevents PARP-1-dependent AIF release. Cells with reduced levels of AIF are resistant to PARP-1-dependent cell death and PAR polymer cytotoxicity. These results reveal PAR polymer as an AIF-releasing factor that plays important roles in PARP-1-dependent cell death.
A receptor-binding region in human choriogonadotropin/lutropin beta subunit. (1987)

Synthetic fragments have not been widely used thus far to evaluate structure-activity relations in the glycoprotein hormones. We prepared a series of peptides representing the intercysteine "loop" sequence (residues 38-57) in human choriogonadotropin (hCG) and lutropin (hLH) beta subunits, anticipating that it might be oriented toward the surface and accessible to receptors. The peptides were characterized chemically and tested for bioactivity by binding to rat ovarian membrane receptor and stimulation of Leydig cell testosterone production. The hCG beta-(38-57) and hLH beta-(38-57) peptides inhibited binding of 125I-labeled hCG half-maximally at 1.51 X 10(-4) and 2.03 X 10(-5) M, respectively, while other peptide hormones and fragments from elsewhere in the beta subunit were inactive. Both peptides stimulated testosterone production, with half-maximal responses at 3.55 X 10(-5) M (hCG) and 2.18 X 10(-5) M (hLH). By radioimmunoassay with an antibody to thyroglobulin-conjugated hCG beta-(38-57) peptide, native hCG and beta subunit were highly reactive, as were the reduced and carboxymethylated subunit and peptide. Helical-wheel projection predicted an amphipathic region in the N-terminal portion of the 38-57 sequence, and circular dichroic measurements showed an increase in ordered structure, especially alpha-helix, when the 38-57 peptides were transferred from an aqueous to a more lipophilic (90% trifluoroethanol) environment. These results indicate that the 38-57 region of beta subunit is exposed on the surface and constitutes a component in the receptor-binding domain for hCG and hLH. A region of amphipathic-helical structure in the 38-57 sequence may promote hormone-receptor interactions in a manner proposed for several other peptide hormones.
Application of Polymerase Chain Reaction with Arbitrary Primers to Strain Identification of Mycoplasma gallisepticum (1995)

DNA heterogeneity among strains and isolates of Mycoplasma gallisepticum (MG) was demonstrated with the arbitrarily primed polymerase chain reaction (AP-PCR) method. This method involves three cycles of low-stringency amplification followed by PCR at higher stringency. Reproducible DNA fragments of 25 different MG strains or isolates were generated with three arbitrarily chosen primers. The MG strains or isolates were distinguished according to the banding patterns of their amplified DNA on agarose gels, and the differences were characteristic for specific isolates. This method is rapid, simple, and reproducible, and it can also be used to determine the similarity between isolates of MG from various sources.
Discovery of Inhibitors of Escherichia coli Methionine Aminopeptidase with the Fe(II)-Form Selectivity and Antibacterial Activity (2008)

Methionine aminopeptidase (MetAP) is a promising target to develop novel antibiotics, because all bacteria express MetAP from a single gene that carries out the essential function of removing N-terminal methionine from nascent proteins. Divalent metal ions play a critical role in the catalysis, and there is an urgent need to define the actual metal used by MetAP in bacterial cells. By high throughput screening, we identified a novel class of catechol-containing MetAP inhibitors that display selectivity for the Fe(II)-form of MetAP. X-ray structure revealed that the inhibitor binds to MetAP at the active site with the catechol coordinating to the metal ions. Importantly, some of the inhibitors showed antibacterial activity at low micromolar concentration on Gram-positive and Gram-negative bacteria. Our data indicate that Fe(II) is the likely metal used by MetAP in the cellular environment, and MetAP inhibitors need to inhibit this metalloform of MetAP effectively to be therapeutically useful.
Adjuvant therapies for colorectal cancer (2007)

结肠和直肠的癌症的管理在最后 25 年戏剧性地变化了。辅助治疗的使用成为了标准实践在局部地先进(阶段 III 和选择阶段 II ) 渲染表面的癌症。改进外科的技术，化学疗法和放射疗法正在导致更高的痊愈率和指向小径为进一步的诺言提供的增生的和 angiogenic 的代理人的发展。这里，我们在冒号和直肠的癌症的切除术以后为本地、远的复发探索风险因素，并且辅佐疗法的角色。为辅助治疗的证据底的讨论愿望焦点在颜色利用了亚群例如的表面的癌症，和治疗老并且阶段 II 疾病。在在复发的减小的直肠的癌症的辅助放射疗法的角色将被探索并且为监视的角色和药品以后的切除术与或没有辅助治疗将也被探讨的最佳的方法。
The induction of ret by Wnt-1 in PC12 cells is atypically dependent on continual Wnt-1 expression. (1996)

Wild type PC12 pheochromocytoma cells that had been infected with a Wnt-1-carrying virus and thus express Wnt-1 (PC12/Wnt-1) are known to acquire the same flat cell phenotype as that of spontaneously occurring PC12 flat cell variants except that the latter do not presently express Wnt-1. Flat cell variants of PC12 cells exhibit markedly altered morphology and gene expression. In order to assess the possibility that the spontaneously occurring flat cell variants could have been induced in wild type PC12 cells by previous transient expression of the cell's endogenous Wnt-1, we have isolated PC12/Wnt-1 cells expressing little or no Wnt-1. In spite of absent Wnt-1 expression, they retained their flat cell morphology, glutamate/aspartate transporter activity, increased neu mRNA levels and lack of both norepinephrine transporter activity and nerve growth factor-induced differentiation. Thus, Wnt-1 expression is not required to maintain the flat cell phenotype. However, we identified one gene, ret, whose mRNA level in PC12 was not only increased by Wnt-1 expression, but whose increased mRNA level was also dependent on continual Wnt-1 expression. This finding suggests that the induction of ret by Wnt-1 can be used to elucidate the Wnt-induced signalling pathway in mammalian cells.
Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas (2009)

The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas.
Attention and the detection of signals. (1980)

Detection of a visual signal requires information to reach a system capable of eliciting arbitrary responses required by the experimenter. Detection latencies are reduced when subjects receive a cue that indicates where in the visual field the signal will occur. This shift in efficiency appears to be due to an alignment (orienting) of the central attentional system with the pathways to be activated by the visual input. It would also be possible to describe these results as being due to a reduced criterion at the expected target position. However, this description ignores important constraints about the way in which expectancy improves performance. First, when subjects are cued on each trial, they show stronger expectancy effects than when a probable position is held constant for a block, indicating the active nature of the expectancy. Second, while information on spatial position improves performance, information on the form of the stimulus does not. Third, expectancy may lead to improvements in latency without a reduction in accuracy. Fourth, there appears to be little ability to lower the criterion at two positions that are not spatially contiguous. A framework involving the employment of a limited-capacity attentional mechanism seems to capture these constraints better than the more general language of criterion setting. Using this framework, we find that attention shifts are not closely related to the saccadic eye movement system. For luminance detection the retina appears to be equipotential with respect to attention shifts, since costs to unexpected stimuli are similar whether foveal or peripheral. These results appear to provide an important model system for the study of the relationship between attention and the structure of the visual system.
Studies on Scutellariae Radix. VII. Anti-arthritic and anti-inflammatory actions of methanolic extract and flavonoid components from Scutellariae Radix. (1984)

A 70% methanol extract of Scutellariae Radix, the dried root of Scutellaria baicalensis GEORGI, and its main flavonoid components, baicalin, baicalein and wogonin, have been screened in comparison with three standard anti-inflammatory agents, phenylbutazone, indomethacin and dexamethasone, for activity in various experimental models of inflammation. All of the test substances were found to inhibit an increase in vascular permeability in mice induced by acetic acid and to reduce acute paw edema in rats induced by compound 48/80. They also suppressed the secondary lesion in developing adjuvant-induced arthritis in rats. Since these substances from Scutellariae Radix were found to be effective in both the acute and chronic phases of inflammation, the crude drug Scutellariae Radix can be considered as having anti-inflammatory activity.
REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters (2020)

An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease, and golden hamsters, which may model more severe disease. We demonstrate that REGN-COV-2 can greatly reduce virus load in the lower and upper airways and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically in rhesus macaques. Similarly, administration in hamsters limits weight loss and decreases lung titers and evidence of pneumonia in the lungs. Our results provide evidence of the therapeutic potential of this antibody cocktail.
VOLATILE PLANT CHEMICALS AND THEIR EFFECT ON HOST PLANT FINDING BY THE CABBAGE ROOT FLY (DELIA BRASSICAE) (1978)

Volatile plant chemicals are generally credited with a major role in host plant location by many phytophagous insects. Mixtures of volatiles are produced in cruciferous plants mainly by the hydrolysis of non‐volatile glucosinolates to volatile isothiocyanates, thiocyanates and nitriles. The cabbage root fly attacks a wide range of cruciferous plants, with differing odours, implying that several volatile chemicals are probably involved in attracting the flies and in stimulating them to lay. Oviposition by the cabbage root fly was studied, therefore, on a large range of wild and cultivated plants to determine the most preferred species. The volatile chemicals in these species were identified in the hope that some of them may prove more useful as attractants for luring cabbage root flies to field traps. Similar volatile chemicals were released from both intact and macerated plants. It was deduced that any one, or combinations, of eleven chemicals may probably be involved in attraction and host plant selection by this fly. The concentrations of these chemicals change during the life of the plant, however, and an initially attractive chemical can become so concentrated that eventually it repels the insect. Difficulties encountered in experiments on olfaction and possible ways in which they can be overcome are discussed. RÉSUMÉ INFLUENCE DES SUBSTANCES CHIMIQUES VOLATILES DUR LA DECOUVERTE DES PLANTES HOTES PAR LA MOUCHE DU CHOU (DELIA BRASSICA) Les substances volatiles des végétaux sont considérées comme jouant un rôle capital dans la découverte de la plante hôte. L'hydrolyse des glucosinolates non volatils en isothiocyanates, thiocyanates et nitriles volatils produit essentiellement les mélanges volatils des Crucifères. Comme la Mouche du Chou attaque une gamme importante de Crucifères aux odeurs différentes, ceci implique que plus d'une substance volatile est probablement impliquée dans l'attraction des mouches et la stimulation de leur ponte. La ponte de la Mouche du Chou a ainsi été étudiée sur de nombreuses plantes sauvages et cultivées pour déterminer les espèces préférées. Les substances volatiles de ces espèces ont été identifiées dans l'espoir que certaines pourraient s'avérer utiles pour attirer les Mouches du Chou dans les pièges. Des substances volatiles semblables ont été libérées par les plantes intactes et macérées. On en a déduit, que l'une quelconque, ou des combinaisons, de 11 substances peuvent être impliquées probablement dans l'attraction et la sélection des plantes hôtes par cette mouche. Cependant leurs concentrations changent pendant la vie de la plante et une substance d'abord attractive peut devenir tellement concentrée qu'elle repousse éventuellement l'insecte. Les difficultés expérimentales de l'olfacation et des méthodes pour les surmonter sont discutées.
An oligo selection procedure for identification of sequence‐specific DNA‐binding activities associated with the plant defence response (1998)

Sequence-specific DNA-binding (SSDB) factors play central roles in transcription, DNA replication, recombination and repair. This report describes a simple procedure for high-throughput identification of SSDB activities without prior knowledge of their target genes or binding sequences. The procedure starts with a population of completely random oligo(nucleotide) sequences and selects for those oligo molecules that specifically bind to cellular SSDB factors by use of common gel-retardation assays and PCR. Amplification and subsequent cloning of these selected oligo molecules result in the establishment of oligo DNA libraries enriched in DNA molecules containing specific sequences recognized by SSDB factors. These oligo libraries can be rapidly screened to identify a large number of SSDB activities, including those that are differentially regulated by developmental and environmental signals. With identified oligo DNA as probes, the corresponding SSDB factors can be isolated and analysed with respect to their structures, regulation and functions. Using this procedure, we have identified approximately 100 SSDB activities from tobacco leaves, including seven that are differentially regulated during the tobacco mosaic virus-induced hypersensitive response in resistant tobacco plants.
Nitric oxide/cGMP pathway signaling actively down-regulates α4β1-integrin affinity: an unexpected mechanism for inducing cell de-adhesion (2011)

We conclude that nitric oxide/cGMP signaling pathway can rapidly down-modulate the affinity state of the VLA-4 binding pocket, especially under the condition of sustained Gαi-coupled GPCR signaling, generated by a non-desensitizing receptor mutant. This suggests a fundamental role of this pathway in de-activation of integrin-dependent cell adhesion.
Detection of circulating fetal nucleic acids: a review of methods and applications (2009)

The discovery of cell-free circulating fetal nucleic acids in maternal plasma has opened up new possibilities in non-invasive prenatal diagnosis. The rapid advancement of this field in the past decade is catalysed by the discovery of new classes of fetal nucleic acid markers and technological developments in nucleic acid detection and amplification. In this review, some of the more significant recent developments in this field will be discussed, including the detection of single molecule, chromosomal aneuploidies, single nucleotide variations and placental microRNAs in maternal plasma.
Steam explosion of biomass to produce durable wood pellets (2011)

Wood pellet is regarded as a clean fuel for combustion with low ash content (less than 1% by weight) and a high heating value around 21500 MJ/m³ compared to a heating value of 5400 MJ/m³ for dry wood chips. However, pellet is easily disintegrated into fines due to impact or moisture sorption during handling and storage. Fines may promote dust explosion during handling or self-heating of pellets in storage. The present study investigates the use of steam explosion pretreatment to improve the pellet durability in terms of mechanical strength and moisture sorption resistance. In this research, a batch steam explosion unit consisting of a steam generator, a steam treatment reactor, and control devices was developed. Steam explosion experiments were carried out on Douglas Fir at 2 temperatures (200°C and 220°C), 2 treatment durations (5 min, 10 min), and 2 particle sizes (0.4 mm and 0.9 mm). It was found that the bulk density and tapped density of steam treated wood increased with the treatment severity. The pellets made with biomass treated at different combinations of temperature-time were 1.4 to 3.3 times stronger than untreated pellets. The steam treated biomass required 12% to 81% more energy to form durable pellets than the untreated biomass. Energy input to produce 45000 metric ton regular pellets and steam exploded pellets was estimated. The input energy ranged from 2.80 to 3.52 MJ/kg. Producing pellets from untreated biomass consumed the least energy while pellets made from biomass treated with saturated steam at 220°C for 10 minutes consumed the highest. A kinetic model for pseudolignin formation during steam explosion was developed. Based on the experimental data in this research and published literature, it was postulated that the creation of pseudolignin is responsible for improved durability of steam exploded pellets. A reaction model was developed to predict the formation of pseudolignin and evaluate the optimized treatment condition for making durable and water repellent wood pellets.
Decentralized autonomous AGV system for material handling (2002)

Decentralized control of an autonomous automated guided vehicle system (AGVS) used for material handling is expected to lead to high system flexibility and robustness. A complete control methodology for decentralized autonomous AGVS control was developed and implemented in a computer-integrated manufacturing environment. The methodology addresses all aspects of AGVS functionality: system management, navigation and load transfer. Hierarchical fuzzy behaviour-based control, a reactive navigation scheme, was expanded to multirobot control in semistructured environments by incorporating a priori path optimization and right-of-the-way determination.