gebhart/patrepeval huggingface dataset:
Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition toN-Activated Pyridines (2012)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTSynthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition to N-Activated PyridinesJames A. Bull‡, James J. Mousseau§, Guillaume Pelletier†, and André B. Charette*†View Author Information† Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Downtown, Montréal, Québec, Canada H3C 3J7‡ Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, U.K.§ Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA*Phone: (514) 343-6283. Fax: (514) 343-5900. E-mail: [email protected]Cite this: Chem. Rev. 2012, 112, 5, 2642–2713Publication Date (Web):February 21, 2012Publication History Received7 July 2011Published online21 February 2012Published inissue 9 May 2012https://pubs.acs.org/doi/10.1021/cr200251dhttps://doi.org/10.1021/cr200251dreview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views27832Altmetric-Citations761LEARN 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 SUBJECTS:Cations,Pyridines,Reagents,Salts,Substitution reactions Get e-Alerts
Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer (2015)

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer.
Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. (1986)

The presence of nerve growth factor (NGF) mRNA and protein in the rat central nervous system is documented. Blot-hybridization analysis showed an abundance of NGF mRNA in the hippocampus, cerebral cortex, and olfactory bulb. Enzyme immunoassay confirmed significant levels of a NGF-like protein in the hippocampus and cerebral cortex. Bioassay of a NGF-like immunoaffinity-purified protein from these regions was physiologically indistinguishable from NGF. Immunohistochemistry revealed a widespread distribution of NGF-like reactivity in the adult brain, preferentially in fiber tracts. NGF mRNA accumulation began at birth, with adult levels reached 3 weeks postnatally. Enzyme immunoassay detected the presence of a NGF-like protein in the embryonic rat brain. Postnatally, the level of NGF-like protein reached a maximum at 3 weeks. Additionally, a distinct fetal form of NGF may exist.
The Pathway via D-Galacturonate/L-Galactonate Is Significant for Ascorbate Biosynthesis in Euglena gracilis (2008)

We have previously proposed that Euglena gracilis possesses a pathway for the production of ascorbate (AsA) through d-galacturonate/L-galactonate as representative intermediates ( Shigeoka, S., Nakano, Y., and Kitaoka, S. (1979) J. Nutr. Sci. Vitaminol. 25, 299-307 ). However, genetic evidence proving that the pathway exists has not been obtained yet. We report here the identification of a gene encoding aldonolactonase, which catalyzes a penultimate step of the biosynthesis of AsA in Euglena. By a BLAST search, we identified one candidate for the enzyme having significant sequence identity with rat gluconolactonase, a key enzyme for the production of AsA via d-glucuronate in animals. The purified recombinant aldonolactonase expressed in Escherichia coli catalyzed the reversible reaction of L-galactonate and L-galactono-1,4-lactone with zinc ion as a cofactor. The apparent K(m) values for L-galactonate and L-galactono-1,4-lactone were 1.55 +/- 0.3 and 1.67 +/- 0.39 mm, respectively. The cell growth of Euglena was arrested by silencing the expression of aldonolactonase through RNA interference and then restored to the normal state by supplementation with L-galactono-1,4-lactone. Euglena cells accumulated more AsA on supplementation with d-galacturonate than d-glucuronate. The present results indicate that aldonolactonase is significant for the biosynthesis of AsA in Euglena cells, which predominantly utilize the pathwayviad-galacturonate/L-galactonate. The identification of aldonolactonase provides the first insight into the biosynthesis of AsA via uronic acids as the intermediate in photosynthetic algae including Euglena.
Cloning of Five Human Cadherins Clarifies Characteristic Features of Cadherin Extracellular Domain and Provides Further Evidence for Two Structurally Different Types of Cadherin (1994)

The entire coding sequences for five possible human cadherins, named cadherin-4, -8, -11, -12 and -13, were determined. The deduced amino acid sequences of cadherin-4 and cadherin-13 showed high homology with those of chicken R-cadherin or chicken T-cadherin, suggesting that cadherin-4 and cadherin-13 are mammalian homologues of the chicken R-cadherin or T-cadherin. Comparison of the extracellular domain of these proteins with those of other cadherins and cadherin-related proteins clarifies characteristic structural features of this domain. The domain is subdivided into five subdomains, each of which contains a cadherin-specific motif characterized by well-conserved amino acid residues and short amino acid sequences. Moreover, each subdomain has unique features of its own. The comparison also provides additional evidence for two structurally different types of cadherins: the first type includes B-, E-, EP-, M, N-, P- and R-cadherins and cadherin-4; the second type includes cadherin-5 through cadherin-12. Cadherin-13 lacks the sequence corresponding to the cytoplasmic domain of typical cadherins, but the extracellular domain shares most of the features common to the extracellular domain of cadherins, especially those of the first type of cadherins, suggesting that cadherin-13 is a special type of cadherin. These results, and those of other recent cloning studies, indicate that many cadherins with different properties are expressed in various tissues of different organisms.
Mechanism of ketol acid reductoisomerase. Steady-state analysis and metal ion requirement (1989)

Ketol acid reductoisomerase is an enzyme of the branched-chain amino acid biosynthetic pathway. It catalyzes two separate reactions: an acetoin rearrangement and a reduction. This paper reports on the purification of the enzyme from a recombinant Escherichia coli and on the steady-state kinetics of the enzyme. The kinetics of the reaction were determined for the forward and reverse reaction by using the appropriate chiral substrates. At saturating metal ion concentrations the mechanism follows an ordered pathway where NADPH binds before acetolactate. The product of the rearrangement of acetolactate, 3-hydroxy-3-methyl-2-oxobutyrate, is shown to be kinetically competent as an intermediate in the enzyme-catalyzed reaction. Starting with acetolactate, Mg2+ is the only divalent metal ion that will support enzyme catalysis. For the reduction of 3-hydroxy-3-methyl-2-oxobutyrate, Mn2+ is catalytically active. Product and dead-end inhibition studies indicate that the binding of metal ion and NADPH occurs randomly. In the forward reaction direction, the deuterium kinetic isotope effect on V/K is 1.07 when acetolactate is the substrate and 1.39 when 3-hydroxy-3-methyl-2-oxobutyrate is the substrate.
The complete (3‐D) surface displacement field in the epicentral area of the 1999 MW7.1 Hector Mine Earthquake, California, from space geodetic observations (2001)

We use Interferometric Synthetic Aperture Radar (InSAR) data to derive continuous maps for three orthogonal components of the co‐seismic surface displacement field due to the 1999 M w 7.1 Hector Mine earthquake in southern California. Vertical and horizontal displacements are both predominantly antisymmetric with respect to the fault plane, consistent with predictions of linear elastic models of deformation for a strike‐slip fault. Some deviations from symmetry apparent in the surface displacement data may result from complexity in the fault geometry.
Rabbit Serum Paraoxonase 3 (PON3) Is a High Density Lipoprotein-associated Lactonase and Protects Low Density Lipoprotein against Oxidation (2000)

The paraoxonase gene family contains at least three members: PON1, PON2, and PON3. The physiological roles of the corresponding gene products are still uncertain. Until recently, only the serum paraoxonase/arylesterase (PON1) had been purified and characterized. Here we report the purification, cloning, and characterization of rabbit serum PON3. PON3 is a 40-kDa protein associated with the high density lipoprotein fraction of serum. In contrast to PON1, PON3 has very limited arylesterase and no paraoxonase activities but rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). These differences facilitated the complete separation of PON3 from PON1 during purification. PON3 hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents. We cloned PON3 from total rabbit liver RNA and expressed it in mammalian 293T/17 cells. The recombinant PON3 has the same apparent molecular mass and substrate specificity as the enzyme purified from serum. Rabbit serum PON3 is more efficient than rabbit PON1 in protecting low density lipoprotein from copper-induced oxidation. This is the first report that identifies a second PON enzyme in mammalian serum and the first to describe an enzymatic activity for PON3.
HAEMATOPORPHYRIN-TREATED MURINE LYMPHOCYTES: IN VITRO INHIBITION OF DNA SYNTHESIS AND LIGHT-MEDIATED INACTIVATION OF CELLS RESPONSIBLE FOR GVHR (1981)

Abstract— It has been known that haemoatoporphyrin derivative (Hpd) has a preferential distribution in tissues with high mitotic index. Furthermore, cytocidal activity of light activated Hpd within the cells has been exploited in the therapy of experimental and human cancer. It is reported here that maximum, long lasting, although reversible, inhibition of DNA synthesis was obtained in Hpd-treated lymphocytes. However, Hpd-treated lymphoid cells did not stimulate allogeneic lymphocytes in the primary mixed lymphocyte reaction (MLR) culture. Phytohaemagglutinin (PHA) stimulated murine lymphocytes treated with Hpd and exposed to laser light have shown higher susceptibility to lysis than resting, PHA unstimulated, lymphocytes. In vitro DBA/2 stimulated C57 lymphocytes, inoculated into X-irradiated BD2F1 mice, upon Hpd treatment followed by exposure to light, did not cause a lethal graft vs. host reaction (GVHR). Haematoporphyrin derivative was preferentially incorporated by large and metabolically active cells. inhibited the incorporation of [3H]-thymidine in the lymphocyte nucleus and could be exploited to selectively remove blast cells from resting lymphocytes.
Dynamics of human replication factors in the elongation phase of DNA replication (2007)

In eukaryotic cells, DNA replication is carried out by coordinated actions of many proteins, including DNA polymerase delta (pol delta), replication factor C (RFC), proliferating cell nuclear antigen (PCNA) and replication protein A. Here we describe dynamic properties of these proteins in the elongation step on a single-stranded M13 template, providing evidence that pol delta has a distributive nature over the 7 kb of the M13 template, repeating a frequent dissociation-association cycle at growing 3'-hydroxyl ends. Some PCNA could remain at the primer terminus during this cycle, while the remainder slides out of the primer terminus or is unloaded once pol delta has dissociated. RFC remains around the primer terminus through the elongation phase, and could probably hold PCNA from which pol delta has detached, or reload PCNA from solution to restart DNA synthesis. Furthermore, we suggest that a subunit of pol delta, POLD3, plays a crucial role in the efficient recycling of PCNA during dissociation-association cycles of pol delta. Based on these observations, we propose a model for dynamic processes in elongation complexes.
Calcium Channel Blockers Differentially Modulate Cytokine Production by Peripheral Blood Mononuclear Cells (2010)

Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent.
Crystal structures of Escherichia coli dihydrofolate reductase: the NADP+ holoenzyme and the folate .cntdot. NADP+ ternary complex. substrate binding and a model for the transition state (1990)

The crystal structure of dihydrofolate reductase (EC 1.5.1.3) from Escherichia coli has been solved as the binary complex with NADP+ (the holoenzyme) and as the ternary complex with NADP+ and folate. The Bragg law resolutions of the structures are 2.4 and 2.5 A, respectively. The new crystal forms are nonisomorphous with each other and with the methotrexate binary complex reported earlier [Bolin, J. T., Filman, D. J., Matthews, D. A., Hamlin, R. C., & Kraut, J. (1982) J. Biol. Chem. 257, 13650-13662]. In general, NADP+ and folate binding conform to predictions, but the nicotinamide moiety of NADP+ is disordered in the holoenzyme and ordered in the ternary complex. A mobile loop (residues 16-20) involved in binding the nicotinamide is also disordered in the holoenzyme. We report a detailed analysis of the binding interactions for both ligands, paying special attention to several apparently strained interactions that may favor the transition state for hydride transfer. Hypothetical models are presented for the binding of 7,8-dihydrofolate in the Michaelis complex and for the transition-state complex.
Visible‐Light‐Activated Molecular Switches (2015)

The ability to influence key properties of molecular systems by using light holds much promise for the fields of materials science and life sciences. The cornerstone of such systems is molecules that are able to reversibly photoisomerize between two states, commonly referred to as photoswitches. One serious restriction to the development of functional photodynamic systems is the necessity to trigger switching in at least one direction by UV light, which is often damaging and penetrates only partially through most media. This review provides a summary of the different conceptual strategies for addressing molecular switches in the visible and near-infrared regions of the optical spectrum. Such visible-light-activated molecular switches tremendously extend the scope of photoswitchable systems for future applications and technologies.
IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition (2016)

IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch-Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen-free environment had less IgA deposition. However, serum IgA of specific pathogen-free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α1KI, and even J chain-deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post-translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.
Cubic phases of garnet-type Li7La3Zr2O12: the role of hydration (2013)

We address the controversial issue of the structural stability of Li7La3Zr2O12 garnets, focusing on the mechanisms that result in the transformation from tetragonal to cubic symmetry. We show that undoped tetragonal Li7La3Zr2O12 not exposed to humidity at any moment undergoes a reversible phase transition to cubic symmetry at Tc ≃ 645 °C that we ascribe to lithium dynamic effects. On the other hand, a close correlation has been found between the appearance of a cubic phase between 100 and 200 °C in X-ray diffractograms and the presence of water, either in the atmosphere in which experiments are performed or already in the starting material. The natures of the high and low-temperature cubic garnets are totally different: the one found above the phase transition does not involve any change in the stoichiometry, whereas the cubic phase formed at low temperature is a hydrated, lithium defective phase, due to the combined effect of water insertion into the garnet structure and the H+/Li+ exchange mechanism. Differences in the actual compositions of the samples depending on their thermal history are corroborated by TG-MS experiments. Chemical reactions and phases formed along the thermal evolution are elucidated with the help of Raman spectroscopy.
The Use of Western Blot Procedures in the Analysis of Herpes Simplex Virus Proteins (1988)

During the past few years a multitude of different experimental approaches have been developed to assess the interaction between proteins, of which the use of cross-linking agents and immune electrophoresis are the most widespread. With the introduction of blotting techniques by electrophoretic transfer of proteins to filter membranes (Towbin et al., 1979), however, the possibility of assessing protein-protein interactions at molecular level has been extended, especially in the analysis of antibody reactivity and specificity. By the transfer of an exact image of electrophoretically separated proteins to a filter membrane, the Western blot technique offers a series of advantages in comparison with other techniques, the most obvious being the ease and practicability of the procedure and the interpretation of results. It is thus that Western blot techniques have also been widely applied to the routine diagnosis of viral infections (e.g. as confirmatory tests in the diagnosis of HIV).
The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules (1998)

The functional sizes of the two streptococcal hyaluronan synthases (HASs) were determined by radiation inactivation analysis of isolated membranes. The native enzymes in membranes from Group A Streptococcus pyogenes HAS and Group C Streptococcus equisimilis HAS were compared with the recombinant proteins expressed in Escherichia coli membranes. Based on their amino acid sequences, the masses of these four proteins as monomers are approximately 48 kDa. In all cases, loss of enzyme activity was a simple single exponential function with increasing radiation dose. The functional sizes calculated from these data were identical for the four HASs at approximately 64 kDa. In contrast, the sizes of the proteins estimated by the loss of antibody reactivity on Western blots were essentially identical at 41 kDa for the four HAS species, consistently lower than the functional size by approximately 23 kDa. Matrix-assisted laser desorption time of flight mass spectrometry analysis of purified S. pyogenes HAS-H6 and S. equisimilis HAS-H6 gave masses that differed by <0.07% from the predicted monomer sizes, which confirms that neither protein is posttranslationally modified or covalently attached to another protein. Ongoing studies indicate that the purified HAS enzymes require cardiolipin (CL) for maximal activity and stability. When irradiated membranes were detergent solubilized and the extracts were incubated with exogenous CL, the residual level of HAS activity increased. Consequently, the calculated functional size decreased by approximately 23 kDa to the expected size of the HAS monomer. The approximately 23-kDa larger size of the functional HAS enzyme, compared with the HAS monomer, is due, therefore, to CL molecules. We propose that the active streptococcal HA synthases are monomers in complex with approximately 16 CL molecules.
Factorized Bilinear Models for Image Recognition (2017)

Although Deep Convolutional Neural Networks (CNNs) have liberated their power in various computer vision tasks, the most important components of CNN, convolutional layers and fully connected layers, are still limited to linear transformations. In this paper, we propose a novel Factorized Bilinear (FB) layer to model the pairwise feature interactions by considering the quadratic terms in the transformations. Compared with existing methods that tried to incorporate complex non-linearity structures into CNNs, the factorized parameterization makes our FB layer only require a linear increase of parameters and affordable computational cost. To further reduce the risk of overfitting of the FB layer, a specific remedy called DropFactor is devised during the training process. We also analyze the connection between FB layer and some existing models, and show FB layer is a generalization to them. Finally, we validate the effectiveness of FB layer on several widely adopted datasets including CIFAR-10, CIFAR-100 and ImageNet, and demonstrate superior results compared with various state-of-the-art deep models.