gebhart/patrepeval huggingface dataset:
Heparin‐based nanoparticles (2009)

The combination of nanoparticles and biological molecules is of intense interest because of the synergistic properties offered by such newly synthesized composites. Heparin (HP), conjugated to nanomaterials, has recently been investigated for its chemical and biological properties. HP has a number of biological activities that can be enhanced when composited with nanoparticles. In addition, HP improves the biocompatibility of nanoparticles improving their performance in various biological applications. A variety of recent research combines HP and nanomaterials for a myriad of applications. HP has been conjugated to the surface of the nanoparticles, such as magnetic and metallic nanoparticles, or biodegradable and nondegradable synthetic polymers. HP has also been incorporated into the nanoparticles. There are numerous possibilities for material composites and chemistries that incorporate HP. This opens the door for novel applications ranging from improving anticoagulant activity, for anticancer and antitumor therapy, to tissue engineering and biosensors. This review examines the different possibilities of HP-based nanoparticle composites and their medicinal or biological applications.
An efficient synthesis of pharmacologically active derivatives of 1,3,4-oxadiazoles (2006)

A simple and environmental friendly microwave irradiation method is devised for the synthesis of derivatives of 1,3,4-oxadiazoles viz., 6a-e and 7h-q in 75–90% yield. Structures of the newly synthesised compounds were confirmed by physical, analytical and spectral (ir, 1H and 13C nmr and ms) data and screened for antiinflammatory, anticonvulsant, antidiuretic and antihaemostatic activities. Some of the compounds have shown potent activities.
Mechanistic Investigation of β-Galactosidase-Activated MR Contrast Agents (2007)

We report a mechanistic investigation of an isomeric series of beta-galactosidase-activated magnetic resonance contrast agents. Our strategy focuses on the synthesis of macrocyclic caged-complexes that coordinatively saturate a chelated lanthanide. Enzyme cleavage of the complex results in an open coordination site available for water that creates a detectable MR contrast agent. The complexes consist of a DO3A Gd(III) chelator modified with a galactopyranose at the N-10 position of the macrocycle. We observed significant differences in relaxometric properties and coordination geometry that can be correlated to subtle variations of the linker between the macrocycle and the galactopyranose. After synthesis and purification of the R, S, and racemic mixtures of complexes 1 and 3 and measurement of the hydration number, water residence lifetime, and longitudinal relaxation rates, we propose mechanisms for water exclusion from the lanthanide in the precleavage state. While the stereochemistry of the linker does not influence the agents' properties, the mechanism of water exclusion for each isomer is significantly influenced by the position of modification. Data for one series with a methyl group substituted on the sugar-macrocycle linker at the alpha-position suggests a steric mechanism where the galactopyranose sugar blocks water from the Gd(III) center. In contrast, our observations for a second series with methyl substitution at the beta position of the sugar-macrocycle linker are consistent with a mechanism in which a bidentate anion occupies two available coordination sites of Gd(III) in the precleavage state.
Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study (2017)

The trial did reach its primary objective. L-Carnitine combined with creatine and L-leucine significantly improved the composite score which reflects muscle mass and strength, at the end of the study compared to placebo. The combination showed an increase in mTOR protein level, a driver for increased muscle mass which translated to an improvement in muscle strength. This new combination may provide a potential nutritional intervention to promote muscle growth and improved physical functioning in older adults.
Ortho/para hydrogen converter for rapid deposition matrix isolation spectroscopy (1999)

We describe the construction and operation of a catalyst-bed type device for precooling and equilibrating the ortho/para composition of a hydrogen gas flow. We use this device to vapor deposit millimeters thick cryogenic parahydrogen (pH2) solids which are remarkably transparent [M. E. Fajardo and S. Tam, J. Chem. Phys. 108, 4237 (1998)]. Infrared absorption spectra of solids deposited at pH2 flow rates up to 290 mmol/h (solid thickness growth rates up to 75 μm/min indicate a residual orthohydrogen (oH2) content of less than 0.01%. Gas phase thermal conductivity measurements indicate a residual oH2 content of 0(−0+5)% for flow rates up to 1.9 mol/h. These pH2 solids can be doped readily by simple codeposition of various impurities produced by any of the numerous dopant sources developed in previous matrix isolation spectroscopy (MIS) studies. The long achievable path lengths, and the desirable properties of pH2 as a matrix host, will enable significant new fundamental and practical applications for MIS.
Infection Efficiency of Four Phytophthora infestans Clonal Lineages and DNA-Based Quantification of Sporangia (2015)

The presence and abundance of pathogen inoculum is with host resistance and environmental conditions a key factor in epidemic development. Therefore, several spore-sampling devices have been proposed to monitor pathogen inoculum above fields. However, to make spore sampling more reliable as a management tool and to facilitate its adoption, information on infection efficiency and molecular tools for estimating airborne sporangia concentration are needed. Experiments were thus undertaken in a growth chamber to study the infection efficiency of four clonal lineages of P. infestans (US-8, US-11, US-23, and US-24) by measuring the airborne sporangia concentration and resulting disease intensity. The relationship between the airborne sporangia concentration and the number of lesions per leaf was exponential. For the same concentration, the sporangia of US-23 caused significantly more lesions than the sporangia of the other clonal lineages did. Under optimal conditions, an airborne sporangia concentration of 10 sporangia m-3 for US-23 was sufficient to cause one lesion per leaf, whereas for the other clonal lineages, it took 15 to 25 sporangia m-3 to reach the same disease intensity. However, in terms of diseased leaf area, there was no difference between clonal lineages US-8, US-23 and US-24. Also, a sensitive quantitative real-time polymerase chain reaction (qPCR) tool was developed to quantify P. infestans airborne sporangia with detection sensitivity of one sporangium. The specificity of the qPCR assay was rigorously tested for airborne inoculum and was either similar to, or an improvement on, other published PCR assays. This assay allows rapid and reliable detection and quantification of P. infestans airborne sporangia and thereby, facilitates the implementation of spores-sampling network.
Capturing the Structure of a Catalytic RNA Intermediate: The Hammerhead Ribozyme (1996)

The crystal structure of an unmodified hammerhead RNA in the absence of divalent metal ions has been solved, and it was shown that this ribozyme can cleave itself in the crystal when divalent metal ions are added. This biologically active RNA fold is the same as that found previously for two modified hammerhead ribozymes. Addition of divalent cations at low pH makes it possible to capture the uncleaved RNA in metal-bound form. A conformational intermediate, having an additional Mg(II) bound to the cleavage-site phosphate, was captured by freeze-trapping the RNA at an active pH prior to cleavage. The most significant conformational changes were limited to the active site of the ribozyme, and the changed conformation requires only small additional movements to reach a proposed transition-state.
Formation of the glycan chains in the synthesis of bacterial peptidoglycan (2001)

The main structural features of bacterial peptidoglycan are linear glycan chains interlinked by short peptides. The glycan chains are composed of alternating units of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), all linkages between sugars being beta,1-->4. On the outside of the cytoplasmic membrane, two types of activities are involved in the polymerization of the peptidoglycan monomer unit: glycosyltransferases that catalyze the formation of the linear glycan chains and transpeptidases that catalyze the formation of the peptide cross-bridges. Contrary to the transpeptidation step, for which there is an abundant literature that has been regularly reviewed, the transglycosylation step has been studied to a far lesser extent. The aim of the present review is to summarize and evaluate the molecular and cellullar data concerning the formation of the glycan chains in the synthesis of peptidoglycan. Early work concerned the use of various in vivo and in vitro systems for the study of the polymerization steps, the attachment of newly made material to preexisting peptidoglycan, and the mechanism of action of antibiotics. The synthesis of the glycan chains is catalyzed by the N-terminal glycosyltransferase module of class A high-molecular-mass penicillin-binding proteins and by nonpenicillin-binding monofunctional glycosyltransferases. The multiplicity of these activities in a given organism presumably reflects a variety of in vivo functions. The topological localization of the incorporation of nascent peptidoglycan into the cell wall has revealed that bacteria have at least two peptidoglycan-synthesizing systems: one for septation, the other one for elongation or cell wall thickening. Owing to its location on the outside of the cytoplasmic membrane and its specificity, the transglycosylation step is an interesting target for antibacterials. Glycopeptides and moenomycins are the best studied antibiotics known to interfere with this step. Their mode of action and structure-activity relationships have been extensively studied. Attempts to synthesize other specific transglycosylation inhibitors have recently been made.
Size-controlled long-circulating PICsome as a ruler to measure critical cut-off disposition size into normal and tumor tissues (2011)

Selective disposition of nanocarriers into target tissue is an essential issue in drug delivery. Critical size of nanocarriers (∼150 nm) discriminating the permeability into normal and tumor tissues was determined by the use of size-tunable, polyion complex hollow vesicles (PICsome) as a ruler.
Orai1 calcium channels in the vasculature (2012)

Orai1 was discovered in T cells as a calcium-selective channel that is activated by store depletion. Recent studies suggest that it is expressed and functionally important also in blood vessels, not only because haematopoietic cells can incorporate in the vascular wall but also because Orai1 is expressed and functional in vascular smooth muscle cells and endothelial cells. This article summarises the arising observations in this new area of vascular research and debates underlying issues and challenges for future investigations. The primary focus is on vascular smooth muscle cells and endothelial cells. Specific topics include Orai1 expression; Orai1 roles in store-operated calcium entry and ionic currents of store-depleted cells; blockade of Orai1-related signals by Synta 66 and other pharmacology; activation or regulation of Orai1-related signals by physiological substances and compartments; stromal interaction molecules and the relationship of Orai1 to other ion channels, transporters and pumps; transient receptor potential canonical channels and their contribution to store-operated calcium entry; roles of Orai1 in vascular tone, remodelling, thrombus formation and inflammation; and Orai2 and Orai3. Overall, the observations suggest the existence of an additional, previously unrecognised, calcium channel of the vascular wall that is functionally important particularly in remodelling but probably also in certain vasoconstrictor contexts.
Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies (2012)

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A-class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg(2.39), His(2.43) and Glu(3.46), which makes a polar lock with T(6.37). These alignments and models provide useful tools for understanding class B GPCR function.
Chimeric 3’ flanking regions strongly enhance gene expression in plants (2018)

Plants represent a promising platform for the highly scalable production of recombinant proteins. Previously, we identified the tobacco extensin terminator lacking its intron as an element that reduced transcript read-through and improved recombinant protein production in a plant-based system. In this study, we systematically compared nonreplicating plant expression vectors containing over 20 commonly used or newly identified terminators from diverse sources. We found that eight gene terminators enhance reporter gene expression significantly more than the commonly used 35S and NOS terminators. The intronless extensin terminator provided a 13.6-fold increase compared with the NOS terminator. Combining terminators in tandem produced large synergistic effects, with many combinations providing a >25-fold increase in expression. Addition of the tobacco Rb7 or TM6 matrix attachment region (MAR) strongly enhanced protein production when added to most terminators, with the Rb7 MAR providing the greatest enhancement. Using deletion analysis, the full activity of the 1193 bp Rb7 MAR was found to require only a 463-bp region at its 3' end. Combined terminators and MAR together provided a >60-fold increase compared with the NOS terminator alone. These combinations were then placed in a replicating geminiviral vector, providing a total of >150-fold enhancement over the original NOS vector, corresponding to an estimated yield of 3-5 g recombinant protein per kg leaf fresh weight or around 50% of the leaf total soluble protein. These results demonstrate the importance of 3' flanking regions in optimizing gene expression and show great potential for 3' flanking regions to improve DNA-based recombinant protein production systems.
Potential Anticancer Agents.1 X. Synthesis of Nucleosides Derived from 6-Deoxy-D-glucofuranose (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPotential Anticancer Agents.1 X. Synthesis of Nucleosides Derived from 6-Deoxy-D-glucofuranoseELMER J. REIST, ROLAND R. SPENCER, and B. R. BAKERCite this: J. Org. Chem. 1958, 23, 11, 1753–1757Publication Date (Print):November 1, 1958Publication History Published online1 May 2002Published inissue 1 November 1958https://pubs.acs.org/doi/10.1021/jo01105a048https://doi.org/10.1021/jo01105a048research-articleACS PublicationsRequest reuse permissionsArticle Views86Altmetric-Citations9LEARN 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
Big data: The next frontier for innovation, competition, and productivity (2011)

The amount of data in our world has been exploding, and analyzing large data sets—so-called big data— will become a key basis of competition, underpinning new waves of productivity growth, innovation, and consumer surplus, according to research by MGI and McKinsey's Business Technology Office. Leaders in every sector will have to grapple with the implications of big data, not just a few data-oriented managers. The increasing volume and detail of information captured by enterprises, the rise of multimedia, social media, and the Internet of Things will fuel exponential growth in data for the foreseeable future.
AMPA and NMDA glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey: an immunohistochemical and in situ hybridization study. (1997)

The objective of the present study was to analyze the cellular and subcellular localization of ionotropic glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey. This was achieved by means of immunohistochemistry at light and electron microscopic levels and in situ hybridization histochemistry. Colocalization studies show that nearly all dopaminergic neurons in both the ventral and dorsal tiers of the substantia nigra compacta (SNc-v, SNc-d) and the ventral tegmental area (VTA) are immunoreactive for AMPA (GluR1, GluR2/3, and GluR4) and NMDAR1 receptor subunits, but not for NMDAR2A/B subunits. The immunoreactivity of the receptor subunits is associated mainly with perikarya and dendritic shafts. Apart from the intensity of immunolabeling for the GluR4 subunit, which is quite similar for the different groups of midbrain dopaminergic neurons, the overall intensity of immunostaining for the other subunits is higher in the SNc-v and SNc-d than in the VTA. In line with these observations, in situ hybridization shows that the average level of labeling for the GluR2 and NMDAR1 subunit mRNAs is significantly higher in the SNc-v than in the VTA, and for the NMDAR1 subunit, higher in the SNc-v than in the SNc-d. In contrast, no significant difference was found for the level of GluR1 mRNA labeling among the three groups of midbrain dopaminergic neurons. At the subcellular level in the SNc-v, AMPA (GluR1 and GluR2/3) and NMDAR1 receptor subunit immunoreactivity is preferentially associated with the postsynaptic densities of asymmetric synapses, but occasionally some immunoreactivity is found along nonsynaptic portions of plasma membranes of dendrites. A small number of preterminal axons, axon terminals, and glial cell processes are also immunoreactive. Our observations indicate that the different groups of midbrain dopaminergic neurons in primates exhibit a certain degree of heterogeneity with regard to the level of expression of some ionotropic glutamate receptor subunits. The widespread neuronal and glial localization of glutamate receptor subunits suggests that excitatory amino acids may act at different levels to control the basal activity and, possibly, to participate in the degeneration of midbrain dopaminergic neurons in Parkinson's disease.
Fully developed contact angle change of a droplet in liquid actuated by dielectric force (2012)

The non-saturation phenomenon of contact angle change of a nonconductive droplet in an immiscible dielectric liquid with iso-density is demonstrated using the dielectric force due to the difference of the two dielectric constants. The concentric electrode design permits the dielectric force exerted at various contact angles. The droplet fully develops from 22° to 176° (nearly spherical) in contact angle as the voltages tuned from 0 to 215 Vrms. The contact angle change was found to behave almost linearly with respect to voltage by experiments. The dielectric force in the liquid/liquid interface was further simulated at the aspects of energy distribution, force distribution, and electric fields, found in a good agreement with experimental results.
An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis (2010)

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3(+) T(reg), Tr1 cells, and IL-17-producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3(+) T(reg) compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3(+) T(reg) in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3(+) T(reg) in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3(+) T(reg) that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3(+) T(reg) differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders.