gebhart/patrepeval huggingface dataset:
Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. (1992)

Tumor necrosis factor alpha (TNF alpha), a primary mediator of systemic responses to sepsis and infection, can be injurious to the organism when present in excessive quantities. Here we report that two types of naturally occurring soluble TNF receptors (sTNFR-I and sTNFR-II) circulate in human experimental endotoxemia and in critically ill patients and demonstrate that they neutralize TNF alpha-induced cytotoxicity and immunoreactivity in vitro. Utilizing immunoassays that discriminate between total sTNFR-I and sTNFR-I not bound to TNF alpha, we show that sTNFR-I-TNF alpha complexes may circulate even in the absence of detectable free TNF alpha. To investigate the therapeutic possibilities of sTNFR-I, recombinant protein was administered to nonhuman primates with lethal bacteremia and found to attenuate hemodynamic collapse and cytokine induction. We conclude that soluble receptors for TNF alpha are inducible in inflammation and circulate at levels sufficient to block the in vitro cytotoxicity associated with TNF alpha levels observed in nonlethal infection. Administration of sTNFR-I can prevent the adverse pathologic sequelae caused by the exaggerated TNF alpha production observed in lethal sepsis.
Lipolysis of menhaden oil triacylglycerols and the corresponding fatty acid alkyl esters by pancreatic lipase in vitro: a reexamination. (1990)

In order to distinguish between possible fatty acid differences during lumenal lipolysis and cellular absorption, we have reinvestigated the in vitro hydrolysis of menhaden oil and its alkyl esters by pancreatic lipase. For this purpose we incubated menhaden oil or its fatty acid methyl and ethyl esters with porcine pancreatic lipase in the presence of bile salts and determined the composition of the released free fatty acids, monoacylglycerols, diacylglycerols, and residual triacylglycerols, or the free fatty acids and residual alkyl esters, respectively, by thin-layer and gas-liquid chromatography. There was significant discrimination against the delta 4- to delta 7-unsaturated fatty acids of both medium and long chain lengths during the hydrolysis of menhaden oil and its fatty acid ethyl esters. In general, the ethyl esters were hydrolyzed 10-50 times more slowly than the corresponding glyceryl esters, depending on the exact ratio of the two substrate types. None of the triacylglycerols or ethyl esters, however, was completely resistant to hydrolysis resulting in an eventual cleavage of all the alkyl esters and presumably all the primary ester bonds in the triacylglycerol molecules. Since the rate of release of the least resistant fatty acid exceeded that of the most resistant acid by only a factor of 6, it is concluded that in the presence of a large excess of lipase the liberated fatty acids would approach the composition of the dietary alkyl or glyceryl esters, as observed during lumenal lipolysis (Yang, L.-Y., A. Kuksis, and J. J. Myher. 1989. Biochem. Cell Biol. 67: 192-204).
Spores of Clostridium difficile Clinical Isolates Display a Diverse Germination Response to Bile Salts (2012)

Clostridium difficile spores play a pivotal role in the transmission of infectious diarrhoea, but in order to cause disease spores must complete germination and return to vegetative cell growth. While the mechanisms of spore germination are well understood in Bacillus, knowledge of C. difficile germination remains limited. Previous studies have shown that bile salts and amino acids play an important role in regulating the germination response of C. difficile spores. Taurocholate, in combination with glycine, can stimulate germination, whereas chenodeoxycholate has been shown to inhibit spore germination in a C. difficile clinical isolate. Our recent studies of C. difficile sporulation characteristics have since pointed to substantial diversity among different clinical isolates. Consequently, in this study we investigated how the germination characteristics of different C. difficile isolates vary in response to bile salts. By analysing 29 isolates, including 16 belonging to the BI/NAP1/027 type, we show that considerable diversity exists in both the rate and extent of C. difficile germination in response to rich medium containing both taurocholate and glycine. Strikingly, we also show that although a potent inhibitor of germination for some isolates, chenodeoxycholate does not inhibit the germination, or outgrowth, of all C. difficile strains. Finally, we provide evidence that components of rich media may induce the germination of C. difficile spores, even in the absence of taurocholate. Taken together, these data suggest that the mechanisms of C. difficile spore germination in response to bile salts are complex and require further study. Furthermore, we stress the importance of studying multiple isolates in the future when analysing the nutrients or chemicals that either stimulate or inhibit C. difficile spore germination.
Folic Acid Conjugates for Nuclear Imaging of Folate Receptor–Positive Cancer (2010)

The folate receptor (FR) is overexpressed on a variety of tumor types, whereas its distribution in normal tissues and organs is highly limited. Exploration of the utility of the FR revealed its promising potential for targeting with folate-based radiopharmaceuticals. Herein, we report the principle of the FR-targeting strategy and summarize the development of several folic acid radioconjugates useful for SPECT and PET of cancer diseases. The potential applicability of folate radiopharmaceuticals for FR-targeted radionuclide therapy is also discussed.
Hydrogen bonding in the lowest singlet n.pi.* excited state of pyrimidine (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrogen bonding in the lowest singlet n.pi.* excited state of pyrimidineMichael M. Carrabba, Jonathan E. Kenny, William R. Moomaw, John Cordes, and Mary DentonCite this: J. Phys. Chem. 1985, 89, 4, 674–677Publication Date (Print):February 1, 1985Publication History Published online1 May 2002Published inissue 1 February 1985https://pubs.acs.org/doi/10.1021/j100250a023https://doi.org/10.1021/j100250a023research-articleACS PublicationsRequest reuse permissionsArticle Views97Altmetric-Citations20LEARN 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 options Get e-Alerts
No wires attached: Usability challenges in the connected mobile world (2003)

Mobile computing platforms combining small, lightweight, low-power devices with wireless network connectivity enable the performance of familiar tasks in new environments and create opportunities for novel interactions. Since mobility imposes significant cognitive and ergonomic constraints affecting device and application usability, ease of use is central to devices in the fully mobile wirelessly connected (FMWC) world. In this paper, we consider mobility as an attribute both of the computer and the user. We explain the differences between transportable and fully mobile devices, and we contrast applications that are essentially FMWC applications, those that can be adapted to the FMWC context, and those that are unsuitable for it. We discuss the unique challenges to usability for mobile users and devices and their interaction, and we point out the increasingly critical role of usability in the mobile environment.
Photoaligned Nanorod Enhancement Films with Polarized Emission for Liquid‐Crystal‐Display Applications (2017)

Semiconductor nanorods (NR) emit polarized light, which is expected to bring manifold benefits, in terms of brightness and color enhancement, for modern liquid-crystal displays (LCD). In this regard, photoaligned nanorod enhancement films (NREF) for color and polarization conversion for LCD backlights are introduced here. The photoinduced anchoring forces, by the photoalignment layer, stimulate well-ordered self-assembly of NR in the thin polymer films. Green and red emitting NR with a quantum yield of ≈80% are aligned unidirectionally and in-plane, showing a polarization ratio of >7:1 and a degree of polarization of >0.81. The photoalignment technique facilitates the fabrication of mixed and multiple stacked NREF for LCDs, which improves the color gamut and polarization efficiency, and is thus expected to increase the optical efficiency of conventional LCDs by ≈60%.
Advocacy, legal practice and truth (2012)

Have our parliaments or courts ever expressly identified the pursuit of truth as being a court's criterion for being? Or have they preferred either to stay mum or to identify another criterion? My thesis is that almost 200 years ago the New South Wales legislature framed the courts' role in terms of the administration of justice, and that this has since remained the central express criterion.
Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow‐derived macrophages by TH 1 and TH 2 cytokines (1995)

Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase. Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline. NO is important in the bactericidal and cytotoxic activities of macrophages. An equivalent functional role of arginase and its products is not known. We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-gamma (IFN-gamma), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E2 (PGE2). We find that PGE2 and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase. In contrast, the TH1 cytokine IFN-gamma does not induce arginase. Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase. Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase. Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase. The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena. The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH1 and TH2 cytokines, respectively.
Origin of cartilage laminae in MRI (1997)

To understand the origin of the laminated appearance of cartilage in MRI (the magic angle effect), microscopic MRI (mu MRI) experiments were performed at 14-microns pixel resolution on normal canine articular cartilage from the shoulder joints. Two-dimensional images of the spin-spin relaxation time (T2) of the cartilage-bone plug at two angles (0 degree and 55 degrees) were calculated quantitatively. A distinct T2 anisotropy was observed as a function of the cartilage tissue depth. The surface and the deep regions exhibit strong orientational dependence of T2, whereas the upper-middle region exhibits little orientational dependence of T2. These three mu MRI regions correspond approximately to the three histologic zones in cartilage tissue. The results from the bulk T2 measurements agreed with these mu MRI results. Our studies show that the laminated appearance of cartilage in MRI is caused by T2 anisotropy of the tissue. We further suggest that the molecular origin of the T2 anisotropy is the nuclear dipolar interaction. The structure of the cartilage tissue indicates that the collagen meshwork defines this T2 anisotropy. The results show that the T2 anisotropy provides an indirect but sensitive indicator for the orientation of macromolecular structures in cartilage. The clinical implications of this anisotropy are discussed.
High Efficiency Transformation of Cultured Tobacco Cells (1985)

Tobacco calli were transformed at levels up to 50% by cocultivation of tobacco cultured cells with Agrobacterium tumefaciens harboring the binary transfer-DNA vector, pGA472, containing a kanamycin resistance marker. Transformation frequency was dependent on the physiological state of the tobacco cells, the nature of Agrobacterium strain and, less so, on the expression of the vir genes of the tumor-inducing plasmid. Maximum transformation frequency was obtained with exponentially growing plant cells, suggesting that rapid growth of plant cells is an essental factor for efficient transformation of higher plants.
The effect of the iron(III) chelator, desferrioxamine, on iron and transferrin uptake by the human malignant melanoma cell. (1994)

The mechanism of action of the clinically used iron(III) chelator, desferrioxamine (DFO), on preventing iron (Fe) uptake from transferrin (Tf) has been investigated using the human melanoma cell line SK-MEL-28. This investigation was initiated due to the paucity of information on the mechanisms of action of DFO in neoplastic cells and because recent studies have suggested that DFO may be a useful antitumor agent. The effect of DFO was dependent on incubation time. After a 2-h incubation, DFO acted like the extracellular chelators, EDTA and diethylenetriaminepentaacetic acid, because there was little inhibition of 59Fe uptake from Tf. In contrast, after a 24-h incubation, DFO (0.5 mM) efficiently reduced internalized 59Fe uptake from Tf to 18% of the control value. These observations suggested the existence of a kinetic block to the entry of the apochelator to intracellular Fe pools and/or to the exit of the DFO-59Fe complex. Indeed, cellular fractionation demonstrated that, in contrast to the decrease in the percentage of 59Fe in the ferritin and membrane fractions, a marked increase in the percentage of 59Fe present in the ferritin-free cytosol occurred. These observations suggested an accumulation of the DFO-59Fe complex within the cell. The highly lipophilic Fe chelator, pyridoxal isonicotinoyl hydrazone, was far more effective than DFO at preventing 59Fe uptake from Tf, illustrating the importance of membrane permeability for effective Fe chelation. Desferrioxamine at a concentration of 1 mM decreased internalized 125I-Tf uptake to 70% of the control. However, the decrease in 59Fe uptake observed could only be partially accounted for by a decrease in Tf uptake, and it appeared that DFO was chelating 59Fe at an intracellular site consistent with the transit Fe pool. The results are discussed in the context of the use of Fe chelators as effective antineoplastic agents.
Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol (2006)

The kinetics of tramadol enantiomers are stereoselective when doses of the racemic drug are given orally. To document whether the route of administration determines the stereoselective kinetics of tramadol enantiomers, healthy volunteers received 100 mg oral or intravenous doses of racemic tramadol, and serial blood samples were obtained to assay tramadol enantiomers and their main phase I metabolites, O-demethyltramadol and N-demethyltramadol. To assess accurately the involvement of their metabolites in the pharmacokinetics of tramadol, it is essential to determine the rate and extent of the formation of the enantiomers of these metabolites. A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented. Tramadol and O-demethyltramadol were the major compounds detected in plasma after intravenous administration. Nevertheless, the N-demethylation of tramadol showed a significant increase when the oral route was used. After both oral and intravenous doses, the kinetics of the tramadol enantiomers were stereoselective. The AUC for (R )-(+)-tramadol was greater than the AUC for (S)-(-)-tramadol. The formation of N-demethyltramadol also was enantioselective after oral administration of racemic tramadol, with a greater AUC for (R)-(+)-N-demethyltramadol than for (S)-(-)-N-demethyltramadol. In the opposite form, (S)-(-)-O-demethyltramadol was formed faster than (R)-(+)-O-demethyltramadol. The metabolism of tramadol was also route-dependent with a different enantiomeric ratio for tramadol and its main phase I metabolites after intravenous and oral administration. The disposition of N-demethyltramadol was concentration-dependent.
A novel method for planning and visualization of ablation lines for atrial fibrillation treatment (2005)

The most common arrhythmia is atrial fibrillation. Beside surgery, intracardiac catheter ablation is used commonly for curative treatment. Navigation systems have been developed to reduce fluoroscopic time and to provide a more accurate positioning. Within these systems, standard 3D-views are used to show intracardiac catheters and ablated areas. We present a novel method to display spatial relations of catheter, anatomical landmarks and ablation lines in a mapped 2D-view. Furthermore, a planning of desired ablation lines is feasible. The method can be a valuable tool to support navigated ablation procedures for atrial fibrillation treatment.
The pathogenesis of CIDP (2003)

Current knowledge about the pathogenic mechanisms involved in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) supports an autoimmune etiology. Some of the cell and humorally mediated immune responses that contribute to the development of CIDP resemble those implicated in multiple sclerosis (MS). The effector role of circulating antibodies has recently been revisited. In addition, similar to the situation in MS, histopathologic studies support the heterogeneity of disease mechanisms in CIDP, with variants showing axon damage. In addition to intravenous immunoglobulin (IVIg), prednisone, and plasma exchange, immunomodulatory drugs also were used to treat CIDP, although no definitive trial data are available. One class of immunomodulators, interferon beta formulations, has proven efficacy in the treatment of MS, and because of clinical similarities between the two diseases it is attractive to investigate whether some agents that are effective in the treatment of MS would also be effective in CIDP. Preliminary studies have evaluated the effects of interferon beta formulations in the treatment of CIDP, one of which has shown promising results and warrants further investigation.
Selenium incorporation using recombinant techniques (2010)

Using selenomethionine to phase macromolecular structures is common practice in structure determination, along with the use of selenocysteine. Selenium is consequently the most commonly used heavy atom for MAD. In addition to the well established recombinant techniques for the incorporation of selenium in prokaryal expression systems, there have been recent advances in selenium labelling in eukaryal expression, which will be discussed. Tips and things to consider for the purification and crystallization of seleno-labelled proteins are also included.
pH Studies on the Mechanism of the Pyridoxal Phosphate-Dependent Dialkylglycine Decarboxylase (1998)

The pH dependence of the steady-state kinetic parameters for the dialkylglycine decarboxylase-catalyzed decarboxylation-dependent transamination between 2-aminoisobutyrate (AIB) and pyruvate is presented. The pH dependence of methylation and DTNB modification reactions, and spectroscopic properties, is used to augment the assignment of the kinetic pKa's to specific ionizations. The coincidence of pKa values (approximately 7.4) observed in kcat/KAIB, 1/KAIB, Kis for pyruvate, KPLP, and in absorbance and fluorescence titrations demonstrates that AIB is not a sticky substrate. It furthermore suggests that the decarboxylation step, or a conformational isomerization preceding it, limits the rate of the overall catalytic cycle. Coexisting, kinetically distinguishable conformers of DGD-PLP, originating from an alkali metal ion binding site, were previously demonstrated at pH 8.2 for DGD-PLP (Zhou, X., Toney, M. D. Biochemistry 37, 5761-5769). The pKa value of approximately 8.8 observed in kcat, kcat/KAIB, Kd for K+, spectrometric titrations, and the reaction of DGD-PLP with DTNB is tentatively assigned to the conformational change interconverting the two enzyme forms previously characterized. Three pKa's are observed in pH titrations of the DGD-PLP coenzyme absorbance. Individual spectra for the four ionization states are deconvoluted by fitting log-normal curves. All four ionization states have both ketoenamine and enolimine tautomers present. This and a review of spectral data in the literature lead to the conclusion that the pKa of approximately 7.4, which gives the largest spectral changes and controls kcat/KAIB, is not deprotonation of the aldimine nitrogen. Rather, it must be an active site residue whose ionization alters the ratio between ketoenamine and enolimine tautomers.
Preclinical Characterization of A-582941: A Novel α7 Neuronal Nicotinic Receptor Agonist with Broad Spectrum Cognition-Enhancing Properties (2008)

Among the diverse sets of nicotinic acetylcholine receptors (nAChRs), the α7 subtype is highly expressed in the hippocampus and cortex and is thought to play important roles in a variety of cognitive processes.In this review, we describe the properties of a novel biaryl diamine α7 nAChR agonist, A-582941.A-582941 was found to exhibit high-affinity binding and partial agonism at α7 nAChRs, with acceptable pharmacokinetic properties and excellent distribution to the central nervous system (CNS).In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation.A-582941 enhanced cognitive performance in behavioral models that capture domains of working memory, short-term recognition memory, memory consolidation, and sensory gating deficit.A-582941 exhibited a benign secondary pharmacodynamic and tolerability profile as assessed in a battery of assays of cardiovascular, gastrointestinal, and CNS function.The studies summarized in this review collectively provide preclinical validation that α7 nAChR agonism offers a mechanism with potential to improve cognitive deficits associated with various neurodegenerative and psychiatric disorders.