gebhart/patrepeval huggingface dataset:
2-Substituted Aminopyrido[2,3-d]pyrimidin-7(8H)-ones. Structure−Activity Relationships Against Selected Tyrosine Kinases and in Vitro and in Vivo Anticancer Activity (1998)

While engaged in therapeutic intervention against a number of proliferative diseases, we have discovered the 2-aminopyrido[2,3-d]pyrimidin-7(8H)-ones as a novel class of potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 2, a series of analogues bearing variable substituents at the C-2 position and methyl or ethyl at N-8 was made. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr; epidermal growth factor, EGFr) and nonreceptor (c-Src) classes. One of the more thoroughly evaluated members was 63 with IC50 values of 0.079 μM (PDGFr), 0.043 μM (bFGFr), 0.044 μM (EGFr), and 0.009 μM (c-Src). In cellular studies, 63 inhibited PDGF-mediated receptor autophosphorylation in a number of cell lines at IC50 values of 0.026−0.002 μM and proliferation of two PDGF-dependent lines at 0.3 μM. It also caused inhibition of soft agar colony formation in three cell lines that overexpress the c-Src TK, with IC50 values of 0.33−1.8 μM. In in vivo studies against a panel of seven xenograft tumor models with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs, compound 63 produced a tumor growth delay of 10.6 days against the relatively refractory SK-OV-3 ovarian xenograft and also displayed activity against the HT-29 tumor. In rat oral bioavailability studies, compound 63 plasma concentrations declined in a biexponential manner, and systemic plasma clearance was high relative to liver blood flow. Finally, in rat metabolism studies, HPLC chromatography identified two metabolites of 63, which were proved by mass spectrometry and synthesis to be the primary amine (58) and N-oxide (66). Because of the excellent potency of 63 against selected TKs, in vitro and in vivo studies are underway for this compound in additional tumor models dependent upon PDGFr, FGFr, and c-Src to assess its potential for advancement to clinical trials.
A Functional Recombinant Myosin II Lacking a Regulatory Light Chain-Binding Site (1993)

Myosin II, which converts the energy of adenosine triphosphate hydrolysis into the movement of actin filaments, is a hexamer of two heavy chains, two essential light chains, and two regulatory light chains (RLCs). Dictyostelium myosin II is known to be regulated in vitro by phosphorylation of the RLC. Cells in which the wild-type myosin II heavy chain was replaced with a recombinant form that lacks the binding site for RLC carried out cytokinesis and almost normal development, processes known to be dependent on functional myosin II. Characterization of the purified recombinant protein suggests that a complex of RLC and the RLC binding site of the heavy chain plays an inhibitory role for adenosine triphosphatase activity and a structural role for the movement of myosin along actin.
Isomeric differentiation of polycyclic aromatic hydrocarbons using silver nitrate reactive desorption electrospray ionization mass spectrometry (2012)

RATIONALE Polycyclic aromatic hydrocarbons (PAHs) are nonpolar and difficult to detect by desorption electrospray ionization. We present a new detection method based on cationization with silver ions, which has the added advantage of being able to differentiate PAHs with the same mass but different structure. METHODS 9,10‐Diphenylanthracene and triptycene, in addition to four different groups of PAH isomers: (1) anthracene and phenanthrene, (2) pyrene and fluoranthene, (3) benz[ a ]anthracene, benz[ b ]anthracene (tetracene), and chrysene (4) benzo[ a ]pyrene and benzo[ k ]fluoranthene, were deposited on a paper surface and bombarded with methanol droplets containing silver nitrate. The resulting microdroplets entered a quadruple mass spectrometer for mass analysis. RESULTS The mass spectrum shows [PAH] + , [Ag + OH + PAH] + , and [Ag(PAH) n ] + (n = 1, 2) (and [PAH + O 2 ] + in the case of benz[ b ]anthracene) ions. PAHs having a bay structure, such as phenanthrene, showed a different tendency to interact with silver ions from those PAHs having a linear arrangement of the fused benzene rings, such as anthracene. The ratios of the [PAH] + peak intensity to that of [Ag–PAH] + , [Ag + OH + PAH] + , [Ag(PAH) 2 ] + , and [PAH + O 2 ] + were used to differentiate the PAH isomers sharing the same molecular formula with different structures. For isomeric mixtures the [PAH] + to [Ag + OH + PAH] + ratio was found to be the most useful parameter. The uncertainty in the mole fraction of an isomeric mixture was ±0.09, ±0.13, ±0.25, and ±0.1 for phenanthrene‐anthracene, fluoranthene‐pyrene, benz[ a ]anthracene‐chrysene, and benzo[ a ]pyrene‐benzo[ k ]fluoranthene, respectively. CONCLUSIONS A simple method has been developed for the detection of PAHs in desorption electrospray ionization mass spectrometry based on Ag(I) cationization. The method showed a capability to differentiate PAHs isomers (having the same molecular mass) in isomeric mixture with an uncertainty in the mole fraction of about ±0.1. At high inlet temperature and voltage, this method showed better sensitivity but less ability to differentiate between isomeric species. Copyright © 2012 John Wiley &amp; Sons, Ltd.
An Antibody Targeting ICOS Increases Intratumoral Cytotoxic to Regulatory T-cell Ratio and Induces Tumor Regression (2020)

The immunosuppressive tumor microenvironment constitutes a significant hurdle to immune checkpoint inhibitor responses. Both soluble factors and specialized immune cells, such as regulatory T cells (Treg), are key components of active intratumoral immunosuppression. Inducible costimulatory receptor (ICOS) can be highly expressed in the tumor microenvironment, especially on immunosuppressive Treg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we performed immune profiling of samples from tumor-bearing mice and patients with cancer to demonstrate differential expression of ICOS in immune T-cell subsets in different tissues. ICOS expression was higher on intratumoral Treg than on effector CD8 T cells. In addition, by immunizing an <i>Icos</i> knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that bound ICOS from different species. We showed that KY1044 induced sustained depletion of ICOS<sup>high</sup> T cells but was also associated with increased secretion of proinflammatory cytokines from ICOS<sup>low</sup> effector T cells (T<sub>eff</sub>). In syngeneic mouse tumor models, KY1044 depleted ICOS<sup>high</sup> Treg and increased the intratumoral T<sub>Eff</sub>:Treg ratio, resulting in increased secretion of IFNγ and TNFα by T<sub>Eff</sub> cells. KY1044 demonstrated monotherapy antitumor efficacy and improved anti-PD-L1 efficacy. In summary, we demonstrated that using KY1044, one can exploit the differential expression of ICOS on T-cell subtypes to improve the intratumoral immune contexture and restore an antitumor immune response.
ChemInform Abstract: Solvent‐Free Preparation of 5‐(α‐D‐Glucosyloxymethyl)furfural from Isomaltulose—Choline Chloride Melts. (2013)

Abstract The title compound (II), a versatile building block from renewable resources, can be prepared in moderate yields from isomaltulose (I) in a choline chloride melt in the presence of acidic catalysts.
The Mitochondrial Cycle of Arabidopsis Shoot Apical Meristem and Leaf Primordium Meristematic Cells Is Defined by a Perinuclear Tentaculate/Cage-Like Mitochondrion (2008)

Plant cells exhibit a high rate of mitochondrial DNA (mtDNA) recombination. This implies that before cytokinesis, the different mitochondrial compartments must fuse to allow for mtDNA intermixing. When and how the conditions for mtDNA intermixing are established are largely unknown. We have investigated the cell cycle-dependent changes in mitochondrial architecture in different Arabidopsis (Arabidopsis thaliana) cell types using confocal microscopy, conventional, and three-dimensional electron microscopy techniques. Whereas mitochondria of cells from most plant organs are always small and dispersed, shoot apical and leaf primordial meristematic cells contain small, discrete mitochondria in the cell periphery and one large, mitochondrial mass in the perinuclear region. Serial thin-section reconstructions of high-pressure-frozen shoot apical meristem cells demonstrate that during G1 through S phase, the large, central mitochondrion has a tentaculate morphology and wraps around one nuclear pole. In G2, both types of mitochondria double their volume, and the large mitochondrion extends around the nucleus to establish a second sheet-like domain at the opposite nuclear pole. During mitosis, approximately 60% of the smaller mitochondria fuse with the large mitochondrion, whose volume increases to 80% of the total mitochondrial volume, and reorganizes into a cage-like structure encompassing first the mitotic spindle and then the entire cytokinetic apparatus. During cytokinesis, the cage-like mitochondrion divides into two independent tentacular mitochondria from which new, small mitochondria arise by fission. These cell cycle-dependent changes in mitochondrial architecture explain how these meristematic cells can achieve a high rate of mtDNA recombination and ensure the even partitioning of mitochondria between daughter cells.
Gentherapie durch einen RGD-modifizierten, hTERT-regulierten, TRAIL-exprimierenden adenoviralen Vektor in malignen Tumoren (2004)

Our results suggest that Ad/TRAIL-F/RGD may become a potent therapeutic agent for the treatment of different human solid carcinomas.
Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing β-oxidation in skeletal muscle (2004)

Stearoyl-CoA desaturase (SCD) has recently been shown to be a critical control point of lipid partitioning and body weight regulation. Lack of SCD1 function significantly increases insulin sensitivity in skeletal muscles and corrects the hypometabolic phenotype of leptin-deficient ob/ob mice, indicating the direct antilipotoxic action of SCD1 deficiency. The mechanism underlying the metabolic effects of SCD1 mutation is currently unknown. Here we show that SCD1 deficiency reduced the total ceramide content in oxidative skeletal muscles (soleus and red gastrocnemius) by approximately 40%. The mRNA levels and activity of serine palmitoyltransferase (SPT), a key enzyme in ceramide synthesis, as well as the incorporation of [14C]palmitate into ceramide were decreased by approximately 50% in red muscles of SCD1-/- mice. The content of fatty acyl-CoAs, which contribute to de novo ceramide synthesis, was also reduced. The activity and mRNA levels of carnitine palmitoyltransferase I (CPT I) and the rate of beta-oxidation were increased in oxidative muscles of SCD1-/- mice. Furthermore, SCD1 deficiency increased phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK activation may be partially responsible for the increased fatty acid oxidation and decreased ceramide synthesis in red muscles of SCD1-/- mice. SCD1 deficiency also reduced SPT activity and ceramide content and increased AMPK phosphorylation and CPT I activity in muscles of ob/ob mice. Taken together, these results indicate that SCD1 deficiency reduces ceramide synthesis by decreasing SPT expression and increasing the rate of beta-oxidation in oxidative muscles.
Task Force on Sudden Cardiac Death of the European Society of Cardiology (2001)

This comprehensive, educational document on sudden cardiac death is an extensive review that was deemed necessary for two reasons: first, major studies have advanced our knowledge of the natural history, risk prediction and evaluation, and prevention of tachyarrhythmias and sudden death in patients with coronary artery disease or heart failure; second, in rare or previously unknown diseases, the recognition of high risk patients is more difficult since studies are either lacking or they are less likely to be performed.
Efficient Markov Chain Monte Carlo Methods for Decoding Neural Spike Trains (2010)

Stimulus reconstruction or decoding methods provide an important tool for understanding how sensory and motor information is represented in neural activity. We discuss Bayesian decoding methods based on an encoding generalized linear model (GLM) that accurately describes how stimuli are transformed into the spike trains of a group of neurons. The form of the GLM likelihood ensures that the posterior distribution over the stimuli that caused an observed set of spike trains is log concave so long as the prior is. This allows the maximum a posteriori (MAP) stimulus estimate to be obtained using efficient optimization algorithms. Unfortunately, the MAP estimate can have a relatively large average error when the posterior is highly nongaussian. Here we compare several Markov chain Monte Carlo (MCMC) algorithms that allow for the calculation of general Bayesian estimators involving posterior expectations (conditional on model parameters). An efficient version of the hybrid Monte Carlo (HMC) algorithm was significantly superior to other MCMC methods for gaussian priors. When the prior distribution has sharp edges and corners, on the other hand, the "hit-and-run" algorithm performed better than other MCMC methods. Using these algorithms, we show that for this latter class of priors, the posterior mean estimate can have a considerably lower average error than MAP, whereas for gaussian priors, the two estimators have roughly equal efficiency. We also address the application of MCMC methods for extracting nonmarginal properties of the posterior distribution. For example, by using MCMC to calculate the mutual information between the stimulus and response, we verify the validity of a computationally efficient Laplace approximation to this quantity for gaussian priors in a wide range of model parameters; this makes direct model-based computation of the mutual information tractable even in the case of large observed neural populations, where methods based on binning the spike train fail. Finally, we consider the effect of uncertainty in the GLM parameters on the posterior estimators.
Stress measurement in East Asian lacquer thin films owing to changes in relative humidity using phase-shifting interferometry (2010)

In this paper, we address the behaviour of lacquer coatings similar to that found on the Mazarin Chest, an important Japanese lacquerware artefact currently held by the Victoria and Albert Museum (V&amp;A) in London. The response of Japanese lacquer ( urushi ) to changes in environmental conditions was investigated by examining the deflection of a glass substrate coated with a thin film of urushi subjected to changes of humidity. This deflection, measured using phase-shifting interferometry, was then used to determine the two in-plane hygral stress components. Results were compared for two sample conditioning regimes—subjected to intense UV ageing and no ageing—each at a range of relative humidity (RH) steps. The changes in humidity were found to cause rapid stress changes in the lacquers, which then relax over much longer time scales. A simple one-dimensional model of the moisture transport and the stress development is shown to be effective in describing the response of the material to changes in environmental RH.
Electroreduction of CO2 to Formate with Low Overpotential Using Cobalt Pyridine Thiolate Complexes (2020)

Electrocatalytic CO2 reduction to value-added products provides a viable alternative to the use of carbon sources derived from fossil fuels. Nevertheless, the ability to carry out these transformations at reasonable energetic costs, e.g. with low overpotential, remains a significant challenge. Molecular catalysts offer a great option in this context, as fine control of their activity and selectivity can be obtained via the tuning of their coordination sphere and ligand set. To this end, we investigated here a series of cheap cobalt(III) pyridine-thiolate complexes as electrocatalysts for CO2 reduction. The effect of the ligands and proton sources on activity was examined. We were able to identify [bipyridine-bis-(2-pyridinethiolato)-cobalt(III)-hexaflurophosphate] as a highly selective catalyst for formate production operating at a very low overpotential of 110 mV to achieve a TOF of 10 s-1. Detailed electrokinetic analysis coupled with density functional theory allowed establishing a mechanistic pathway for these catalysts, highlighting the role of key metal hydride intermediates. The catalysts deactivate via the formation of stable Co carbonyl complexes, but we demonstrated that the active species could be regenerated upon oxidation and release of coordinated CO ligands.
Mixed Confidence Estimation for Iterative CT Reconstruction (2016)

Dynamic (4D) CT imaging is used in a variety of applications, but the two major drawbacks of the technique are its increased radiation dose and longer reconstruction time. Here we present a statistical analysis of our previously proposed Mixed Confidence Estimation (MCE) method that addresses both these issues. This method, where framed iterative reconstruction is only performed on the dynamic regions of each frame while static regions are fixed across frames to a composite image, was proposed to reduce computation time. In this work, we generalize the previous method to describe any application where a portion of the image is known with higher confidence (static, composite, lower-frequency content, etc.) and a portion of the image is known with lower confidence (dynamic, targeted, etc). We show that by splitting the image space into higher and lower confidence components, MCE can lower the estimator variance in both regions compared to conventional reconstruction. We present a theoretical argument for this reduction in estimator variance and verify this argument with proof-of-principle simulations. We also propose a fast approximation of the variance of images reconstructed with MCE and confirm that this approximation is accurate compared to analytic calculations of and multi-realization image variance. This MCE method requires less computation time and provides reduced image variance for imaging scenarios where portions of the image are known with more certainty than others allowing for potentially reduced radiation dose and/or improved dynamic imaging.
Phosphorylation of rat hepatic fructose-1,6-bisphosphatase and pyruvate kinase. (1980)

Fructose-1,6-bisphosphatase from rat liver was phosphorylated with cyclic AMP-dependent protein kinase and [gamma-32P]ATP. Brief exposure of the 32P-labeled enzyme to trypsin removed all radioactivity from the enzyme core and produced a single-labeled peptide. The partial sequence of the 17-amino acid peptide was found to be Ser-Arg-Pro-Ser(P)-Leu-Pro-Leu-Pro-(Ser2, Glx2, Pro2, Leu, Arg2). The kinetics of cyclic AMP-dependent protein kinase-catalyzed phosphorylation of native fructose bisphosphatase were compared with those of rat liver type L pyruvate kinase where the sequence around the phosphoserine is known (Arg-Arg-Ala-Ser(P)-Val; Hjelmquist, G., Anderson, J., Edlund, B., and Engstrom, L. (1974) Biochem. Biophys. Res. Commun. 61, 559-563). The Km for pyruvate kinase (17 microM) was less than that for fructose bisphosphatase (58 microM); the Vmax was about 3-fold greater with pyruvate kinase as substrate. The relationship between the rates of phosphorylation of these native substrates and the amino acid sequences surrounding the phosphorylated sites is discussed.
Serum procalcitonin in pulmonary tuberculosis. (2011)

In West African PTB patients, PCT levels were low but increased significantly with increasing severity of disease, and can predict mortality risk.
Lanthanide-Containing 22-Tungsto-2-germanates [Ln(GeW11O39)2]13–: Synthesis, Structure, and Magnetic Properties (2020)

We report on the synthesis and structural characterization of two series of lanthanide-containing 22-tungsto-2-germanates. The first series corresponds to a family of polyanions with the formula [Ln(<i>β</i><sub><i>2</i></sub>-GeW<sub>11</sub>O<sub>39</sub>)<sub>2</sub>]<sup>13-</sup> (Ln<sup>III</sup> = La (<b>1</b>), Ce (<b>2</b>), Pr (<b>3</b>), Nd (<b>4</b>), Sm (<b>5</b>), Gd (<b>6</b>), Dy (<b>7</b>)), and the second series corresponds to a family with the formula [Ln(<i>β</i><sub><i>2</i></sub>-GeW<sub>11</sub>O<sub>39</sub>)(α-GeW<sub>11</sub>O<sub>39</sub>)]<sup>13-</sup> (Ln<sup>III</sup> = Ho (<b>8</b>), Er (<b>9</b>), Tm (<b>10</b>)). All compounds were characterized in the solid state by single-crystal and powder XRD, IR, TGA, and SQUID magnetometry. The polyanions were synthesized in aqueous medium by direct reaction of the monolacunary [<i>β</i><sub><i>2</i></sub>-GeW<sub>11</sub>O<sub>39</sub>]<sup>8-</sup> POM precursor with the corresponding lanthanide salts. The structure of the polyanions consists of an 8-coordinated lanthanide ion in a square-antiprismatic geometry, which is sandwiched either between two [<i>β</i><sub><i>2</i></sub>-GeW<sub>11</sub>O<sub>39</sub>]<sup>8-</sup> units for <b>1</b>-<b>7</b> or between a [<i>β</i><sub><i>2</i></sub>-GeW<sub>11</sub>O<sub>39</sub>]<sup>8-</sup> and a [α-GeW<sub>11</sub>O<sub>39</sub>]<sup>8-</sup> unit for <b>8</b>-<b>10</b>. Furthermore, the effect of the central paramagnetic lanthanide ion on the magnetic behavior of the polyanions was investigated, with the erbium-derivative [Er(<i>β</i><sub><i>2</i></sub>-GeW<sub>11</sub>O<sub>39</sub>)(α-GeW<sub>11</sub>O<sub>39</sub>)]<sup>13-</sup> (<b>9</b>) showing single-molecule magnet (SMM) behavior.
Norepinephrine complexes and reduced vanadium(V) to reverse vanadate inhibition of the (sodium, potassium ion)-dependent ATPase (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNorepinephrine complexes and reduced vanadium(V) to reverse vanadate inhibition of the (sodium, potassium ion)-dependent ATPaseLewis C. Cantley Jr., John H. Ferguson, and Kenneth KustinCite this: J. Am. Chem. Soc. 1978, 100, 16, 5210–5212Publication Date (Print):August 1, 1978Publication History Published online1 May 2002Published inissue 1 August 1978https://pubs.acs.org/doi/10.1021/ja00484a053https://doi.org/10.1021/ja00484a053research-articleACS PublicationsRequest reuse permissionsArticle Views81Altmetric-Citations85LEARN 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
ChemInform Abstract: Synthesis of 4,5‐Bis‐ and 4,4′,5,5′‐Tetrakis(2‐hydroxyethylthio) tetrathiafulvalene: The Assembly of Tris‐ and Pentakis( tetrathiafulvalene) Macromolecules. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.