gebhart/patrepeval huggingface dataset:
5,5-Diarylpenta-2,4-dienoic Acid Amides as Potential Antimalarial Agents (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT5,5-Diarylpenta-2,4-dienoic Acid Amides as Potential Antimalarial AgentsWilliam Colwell, Judy Lange, and David HenryCite this: J. Med. Chem. 1968, 11, 4, 749–752Publication Date (Print):July 1, 1968Publication History Published online26 November 2002Published inissue 1 July 1968https://pubs.acs.org/doi/10.1021/jm00310a604https://doi.org/10.1021/jm00310a604research-articleACS PublicationsRequest reuse permissionsArticle Views106Altmetric-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
Directed Mutagenesis Using the Polymerase Chain Reaction (1997)

This unit contains two basic protocols for introducing base changes into specific DNA sequences. The first describes the incorporation of a restriction site and the second details the generation of specific point mutations. An Alternate Protocol describes generating point mutations by sequential PCR steps. Although the general procedure is the same in all three protocols, there are differences in the design of the synthetic oligonucleotide primers and in the subsequent cloning and analyses of the amplified fragments.
Carbon monoxide released by CORM-3 inhibits human platelets by a mechanism independent of soluble guanylate cyclase (2006)

Inhibition of platelet aggregation by CO released by a novel, water-soluble CORM is not mediated by activation of soluble guanylate cyclase. In contrast to NO and PGI(2), CO effectively inhibits platelets even when cells are activated excessively. We suggest that despite the fact that CO is not a potent inhibitor of platelet activation, it may gain importance when NO and PGI(2) alone are insufficient to overcome excessive platelet activation.
Ocean Bottom Node Seismic: Learnings from Bonga, Deepwater Offshore Nigeria (2012)

The Bonga Main field was discovered by Shell Nigeria Exploration and Production Company (SNEPCO) in 1995 and is located some 120 km offshore Nigeria at water depths of 800m - 1200m. First oil production started in November 2005. Bonga is Nigeria's first deepwater discovery. Oil production is from the main stacked reservoirs (690, 702, 710/740 and 803) through several producer/injector well pairs. The Bonga Main field is covered by a block-wide exploration 3D seismic streamer survey conducted in 2000 which serves as the baseline 4D seismic survey. As part of the Field's Life-Cycle Development Plan, 4D Time Lapse serves as an integral part of the monitoring of the producing reservoirs. Dynamic reservoir modelling predicted that the Bonga reservoirs would be conducive to generating robust time-lapse signals of the water injection sweep and associated fluid movements, with pressure effects expected to be secondary due to the field's pressure maintenance program. Subsequently, a very successful 4D time-lapse seismic streamer monitor survey was acquired over the Bonga Main field in 2008, with the objective of providing early confirmation of fluid movements and reservoir models, for optimum management of the producing reservoirs. Although extremely successful, it became clear that streamer seismic would not be the best future option for imaging the up-dip reservoirs under the FPSO. Subsequently, an Ocean Bottom Node Survey was proposed and acquired in 2010 to serve as an up-dip seismic baseline for future OBN monitors seismic surveys. This paper will give a brief overview of the Bonga 4D streamer seismic results, outline the case for action for acquiring an OBN seismic survey, discuss the design criteria, acquisition and processing of this baseline OBN, and conclude with a comparisons of the OBN to the streamer data, highlighting the associated business implications.
Antiapoptotic and Trophic Effects of Dominant-Negative Forms of Dual Leucine Zipper Kinase in Dopamine Neurons of the Substantia NigraIn Vivo (2008)

There is extensive evidence that the mitogen-activated protein kinase (MAPK) signaling cascade mediates programmed cell death in neurons. However, current evidence that the mixed linage kinases (MLKs), upstream in this cascade, mediate cell death is based, in the in vivo context, entirely on pharmacological approaches. The compounds used in these studies have neither complete specificity nor selectivity among these kinases. Therefore, to better address the molecular specificity of the MLKs in mediating neuron death, we used dominant-negative constructs delivered by AAV (adenoassociated virus) vector transfer. We assessed effects in a neurotoxin model of parkinsonism, in which neuroprotection by pharmacologic MLK inhibition has been reported. We find that two dominant-negative forms of dual leucine zipper kinase (DLK) inhibit apoptosis and enhance long-term survival of dopamine neurons, but a dominant negative of MLK3 does not. Interestingly, the kinase-dead form of DLK not only blocks apoptosis but also has trophic effects on dopamine neurons. Although the MAPK cascade activates a number of downstream cell death mediators, we find that inhibition of DLK correlates closely with blockade of phosphorylation of c-jun and prevention of cell death. We conclude that DLK acts primarily through c-jun phosphorylation to mediate cell death in this model.
Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: comparison with structures of other complexes (1990)

O-[[(1R)-[[N-(Phenylmethoxycarbonyl)-L-alanyl]amino]ethyl] hydroxyphosphinyl]-L-3-phenyllacetate [ZAAP(O)F], an analogue of (benzyloxycarbonyl)-Ala-Ala-Phe or (benzyloxycarbonyl)-Ala-Ala-phenyllactate, binds to carboxypeptidase A with great affinity (Ki = 3 pM). Similar phosphonates have been shown to be transition-state analogues of the CPA-catalyzed hydrolysis [Hanson, J. E., Kaplan, A. P., & Bartlett, P. A. (1989) Biochemistry 28, 6294-6305]. In the present study, the structure of the complex of this phosphonate with carboxypeptidase A has been determined by X-ray crystallography to a resolution of 2.0 A. The complex crystallizes in the space group P2(1)2(1)2(1) with cell dimensions a = 61.9 A, b = 67.2 A, and c = 76.2 A. The structure of the complex was solved by molecular replacement. Refinement of the structure against 20,776 unique reflections between 10.0 and 2.0 A yields a crystallographic residual of 0.193, including 140 water molecules. The two phosphinyl oxygens of the inhibitor bind to the active-site zinc at 2.2 A on the electrophilic (Arg-127) side and 3.1 A on the nucleophilic (Glu-270) side. Various features of the binding mode of this phosphonate inhibitor are consistent with the hypothesis that carboxypeptidase A catalyzed hydrolysis proceeds through a general-base mechanism in which the carbonyl carbon of the substrate is attacked by Zn-hydroxyl (or Zn-water). An unexpected feature of the bound inhibitor, the cis carbamoyl ester bond at the benzyloxycarbonyl linkage to alanine, allows the benzyloxycarbonyl phenyl ring of the inhibitor to interact favorably with Tyr-198. This complex structure is compared with previous structures of carboxypeptidase A, including the complexes with the potato inhibitor, a hydrated keto methylene substrate analogue, and a phosphonamidate inhibitor. Comparisons are also made with the complexes of thermolysin with some phosphonamidate inhibitors.
Angular-dependent metal-enhanced fluorescence from silver colloid-deposited films: opportunity for angular-ratiometric surface assays (2007)

We describe an exciting opportunity for Metal-Enhanced Fluorescence (MEF)-based surface assays using an angular-ratiometric approach to the observed enhanced emission from fluorophores in close proximity to silver colloids deposited on glass substrates. This approach utilizes the radiationless energy transfer (coupling) between the excited states of the fluorophore and the induced surface plasmons of the silver colloids, and the subsequent angular-dependent fluorescence emission from the fluorophore-silver colloid system. Since MEF is related to surface plasmons' ability to scatter light, angular-dependent light scattering from three different silvered surfaces and glass substrates were investigated using two common excitation angles, 45 and 90 degrees . The scattered light from silvered surfaces with a high loading was observed at wider angles on both sides of the glass substrates, while forward scattering (from the back of the glass) was dominant for the silvered surfaces with low loading, as explained by both Mie and Rayleigh theories. When silver colloids were placed between the fluorophore and glass interface, the coupled fluorescence emission through the higher refractive index glass (and in air), increased in an angular-dependent fashion, following closely the angular-dependent light scattering pattern of the silver colloids themselves. Similar observations for fluorescence emission from fluorophores deposited onto glass surfaces alone were made, but at much narrower angles on both sides of the fluorophore-glass interface and were simply explained by Lambert's cosine law. As the loading of silver on glass was increased, the enhanced fluorescence emission was observed at wider angles (towards 0 and 180 degrees ) at both sides of the silvered surfaces. Glass surfaces without silver colloids were used as control samples to demonstrate the benefits of MEF for enhancing fluorescence signatures in an elegant, angular-dependent fashion. Finally, the utility of the angular-dependent MEF phenomenon for intensity-based angular-ratiometric surface assays is demonstrated.
Cryptographic Message Syntax (CMS) (2009)

This document describes the Cryptographic Message Syntax (CMS). This syntax is used to digitally sign, digest, authenticate, or encrypt arbitrary message content.
The roots of a corporate tax (2010)

Abstract This chapter discusses the roots of the corporate income tax, which can be found in the 19th century. The early taxation of corporations — generally through capital stock taxes, dividend taxes, or similar devices applied to members of particular industries — was neither a punishment nor a price for the special privileges of corporate status. Rather, entity-level taxation developed as an aid to other forms of taxation and as a reflection of the difficulties the corporation posed for these taxes. The state property tax, for example, dealt with the introduction of intangible forms of property and the spread of property beyond local or even state borders by taxing at the entity level to ensure that the tax revenues did not escape the jurisdiction. Similarly, entity-level taxation served as a collection mechanism for dividends paid to shareholders when an income tax was adopted during the Civil War and Reconstruction. In both cases, these early taxes were targeted against members of specific industries rather than corporations per se. Nevertheless, the selection of these particular industries for special taxation was often a reflection of the dominance of the corporate form among their members. In this sense, these taxes were the precursors to the modern corporate income tax.
AN ABUNDANCE OF RNA REGULATORS (2005)

The importance of small, noncoding RNAs that act as regulators of transcription, of RNA modification or stability, and of mRNA translation is becoming increasingly apparent. Here we discuss current knowledge of regulatory RNA function and review how the RNAs have been identified in a variety of organisms. Many of the regulatory RNAs act through base-pairing interactions with target RNAs. The base-pairing RNAs can be grouped into two general classes: those that are encoded on the opposite strand of their target RNAs such that they contain perfect complementarity with their targets, and those that are encoded at separate locations on the chromosome and have imperfect base-pairing potential with their targets. Other regulatory RNAs act by modifying protein activity, in some cases by mimicking the structures of other RNA or DNA molecules.
Mutational analysis of a vaccinia virus intermediate promoter in vivo and in vitro (1990)

The expression of the vaccinia virus intermediate I3 gene depends on trans-acting factors which are present in an active state prior to DNA replication. However, activation of transcription requires DNA replication in cis (J. C. Vos and H. G. Stunnenberg, EMBO J., 7:3487-3492, 1988). We have made deletion and linker scanner mutations of the I3 promoter to determine the sequence requirements for transcriptional activity and the dependence of DNA replication. The I3 promoter appears to consist of two elements which are essential and sufficient for accurate transcription initiation both in vivo and in vitro. An upstream and a downstream sequence element were defined ranging from -20 to -9 and +1 to +9, respectively. The upstream element appears to be highly homologous to a sequence in the intermediate I8 promoter. A 3-bp substitution in the upstream I3 promoter element resulted in a change of transcriptional specificity from intermediate to late. Finally, the mutations did not result in an activation of the intermediate promoter prior to DNA replication.
Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS (2007)

The cellular pathways of motor neuronal injury have been investigated in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis (ALS) using laser-capture microdissection and microarray analysis. The advantages of this study include the following: analysis of changes specifically in motor neurons (MNs), while still detecting effects of interactions with neighboring cells; the ability to profile changes during disease progression, an approach not possible in human ALS; and the use of transgenic mice bred on a homogeneous genetic background, eliminating the confounding effects arising from a mixed genetic background. By using this rigorous approach, novel changes in key cellular pathways have been detected at both the presymptomatic and late stages, which have been validated by quantitative reverse transcription-PCR. At the presymptomatic stage (60 d), MNs extracted from SOD1 G93A mice show a significant increase in expression of genes subserving both transcriptional and translational functions, as well as lipid and carbohydrate metabolism, mitochondrial preprotein translocation, and respiratory chain function, suggesting activation of a strong cellular adaptive response. Mice 90 d old still show upregulation of genes involved in carbohydrate metabolism, whereas transcription and mRNA processing genes begin to show downregulation. Late in the disease course (120 d), important findings include the following: marked transcriptional repression, with downregulation of multiple transcripts involved in transcriptional and metabolic functions; upregulation of complement system components; and increased expression of key cyclins involved in cell-cycle regulation. The changes described in the motor neuron transcriptome evolving during the disease course highlight potential novel targets for neuroprotective therapeutic intervention.
Expression of AMPA receptor subunit flip/flop splice variants in the rat auditory brainstem and inferior colliculus (2001)

The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit mRNAs and their flip/flop splice variants was evaluated in the rat auditory brainstem and inferior colliculus employing in situ hybridization with radiolabeled oligonucleotide probes. A differential expression of AMPA receptor subunits in auditory nuclei was observed. In general, neurons in all nuclei of the auditory brainstem express high levels of GluR-C flop and GluR-D flop mRNA, but low to very low levels of GluR-A and GluR-B mRNA. The strongest GluR-C and -D flop expression is found in the ventral and medial part of the anteroventral cochlear nucleus, the posteroventral cochlear nucleus, and the medial and the lateral superior olive. These nuclei are part of the binaural auditory pathway which is important for sound localization in space. In contrast, neurons in the central nucleus of the inferior colliculus express high levels of GluR-B flip but only low levels of the other AMPA receptor subunits. From our data, we conclude that neurons of nuclei involved in binaural processing exhibit a specific "auditory AMPA receptor" which consists primarily of GluR-C flop and -D flop and often lacks GluR-B subunits; this indicates fast kinetics and high Ca(2+) permeability of AMPA receptor currents. In contrast, neurons in the central nucleus of the inferior colliculus contain large amounts of GluR-B flip subunits resulting in Ca(2+) impermeable AMPA receptors with slow kinetics.
Human skin dendritic cells can be targeted in situ by intradermal injection of antibodies against lectin receptors (2014)

Skin dendritic cells (DC) express C-type lectin receptors for the recognition of pathogens. Langerhans cells (LC) express the receptor Langerin/CD207, whereas DEC-205/CD205 is mainly expressed by dermal DC, but can also be detected at low levels on LC. In this study, we tested an ex vivo approach for targeting DC in situ with monoclonal antibodies (mAb) against Langerin and DEC-205. The targeting mAb was injected intradermally into human skin biopsies or added to the medium during skin explant culture. Corresponding to the expression patterns of these lectin receptors on skin DC, Langerin mAb was detected merely in LC in the epidermis and DEC-205 mainly in dermal DC in human skin explants, regardless of the application route. Migratory skin DC bound and carried targeting mAb from skin explants according to their lectin receptor expression profiles. In contrast to the very selective transport of Langerin mAb by LC, DEC-205 mAb was more widely distributed on all CD1a(+) skin DC subsets but almost absent in CD14(+) dermal DC. As effective vaccination requires the addition of adjuvant, we co-administered the toll-like receptor (TLR)-3 ligand poly I:C with the mAb. This adjuvant enhanced binding of DEC-205 mAb to all skin DC subsets, whereas Langerin targeting efficacy remained unchanged. Our findings demonstrate that LC can be preferentially targeted by Langerin mAb. In contrast, DEC-205 mAb can be bound by all CD1a(+) skin DC subsets. The efficacy of DEC-205 mAb targeting strategy can be boosted by addition of poly I:C underlining the potential of this combination for immunotherapeutical interventions.
Calcium Antagonists Fail to Protect Mammalian Spinal Neurons After Physical Injury (1989)

Most investigations of calcium antagonists as treatments for experimental spinal cord injury (SCI) have not demonstrated significant reduction of tissue damage or improvement in neurologic outcome. Many of these studies were prompted by reports that these agents increase blood flow to ischemic tissues. However, in vitro studies of renal and neuronal tissues subjected to an anoxic stress have shown that the calcium antagonists can confer direct protection on stressed parenchymal cells. We have used a tissue culture model of nerve cell injury to investigate whether calcium antagonists increase the probability of survival of spinal cord neurons after a defined physical trauma. Preliminary toxicity studies determined the maximum nontoxic dosages of verapamil (80 microM), nifedipine (10 microM), and chlorpromazine (10 microM) for neurons in our cultures. Preselected neurons (100-200 per study) were subjected to amputation of one primary dendrite at a distance of 100 microns from the perikaryon. Erythrosine B tests of viability conducted 24 h after lesioning failed to demonstrate that neurons injured in the presence of any one of these agents had an increased probability of survival compared to operated control neurons. Viability evaluations conducted 2 h after injury with phase contrast microscopy showed no evidence of slowed deterioration. Correction for other lesion physical parameters (lesion diameter and the extent of proximal segment retraction) also failed to reveal any increased protection by these agents. We conclude that calcium antagonists alone will not be useful for treatment of the primary injury of SCI.
Human monoclonal anti‐D antibodies. I. THEIR PRODUCTION, SEROLOGY, QUANTITATION AND POTENTIAL USE AS BLOOD GROUPING REAGENTS (1989)

Eight monoclonal IgG antibodies to the Rh antigen D, produced by Epstein-Barr virus transformed B-lymphoblastoid cell lines from two individuals, have been assessed for their suitability as blood grouping reagents. All showed similar specificity and agglutinated all red cells with partial D antigens tested except category DVI cells. They gave strong reactions with Du red cells in indirect antiglobulin tests, and they all gave good reactions with R1R1, R2R2 and R0r cells in manual tests using antiglobulin, enzyme or albumin methods. Initial studies showed that some of the monoclonal antibodies worked well at high dilutions on a Technicon Autogrouper 16C when used for routine D-typing of blood donors. Antibody production by the cell lines was stable for many months in continuous culture. These monoclonal antibodies may be useful diagnostic reagents.
Genomic Localization of a T Serotype Locus to a Recombinatorial Zone Encoding Extracellular Matrix-Binding Proteins in Streptococcus pyogenes (2002)

Streptococcus pyogenes is an important bacterial pathogen afflicting humans. A striking feature is its extraordinary biological diversity, evident in the wide range of diseases it can cause and the antigenic heterogeneity present on its surface. The T antigens form the basis of a major serological typing scheme that is often used as an alternative or supplement to M typing. Unlike M typing, the genetic basis for T typing is poorly understood. In this report, the tee6 gene is localized to a position approximately equal to 3.3 kb downstream from prtF1 (or sfbI), which encodes the Fn-binding protein, protein F, a key virulence factor. Comparison of this portion of the genome with those of four additional strains reveals the presence of genes encoding a collagen-binding protein (Cpa) and a second Fn-binding protein (PrtF2 or PfbpI). This chromosomal region--here designated the FCT region--is approximately 11 to 16 kb in length and is flanked at both ends by long stretches of highly conserved sequence. For each of the five strains, the FCT region contains a unique combination of semiconserved loci, indicative of extensive intergenomic recombination. The data provide evidence that the highly recombinatorial FCT region of the S. pyogenes genome is under strong selection for change in response to the host environment.