gebhart/patrepeval huggingface dataset:
Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult. (1995)

The recently cloned, distant member of the transforming growth factor beta (TGF-beta) family, glial cell line-derived neurotrophic factor (GDNF), has potent trophic actions on fetal mesencephalic dopamine neurons. GDNF also has protective and restorative activity on adult mesencephalic dopaminergic neurons and potently protects motoneurons from axotomy-induced cell death. However, evidence for a role for endogenous GDNF as a target-derived trophic factor in adult midbrain dopaminergic circuits requires documentation of specific transport from the sites of synthesis in the target areas to the nerve cell bodies themselves. Here, we demonstrate that GDNF is retrogradely transported by mesencephalic dopamine neurons of the nigrostriatal pathway. The pattern of retrograde transport following intrastriatal injections indicates that there may be subpopulations of neurons that are GDNF responsive. Retrograde axonal transport of biologically active 125I-labeled GDNF was inhibited by an excess of unlabeled GDNF but not by an excess of cytochrome c. Specificity was further documented by demonstrating that another TGF-beta family member, TGF-beta 1, did not appear to affect retrograde transport. Retrograde transport was also demonstrated by immunohistochemistry by using intrastriatal injections of unlabeled GDNF. GDNF immunoreactivity was found specifically in dopamine nerve cell bodies of the substantia nigra pars compacta distributed in granules in the soma and proximal dendrites. Our data implicate a specific receptor-mediated uptake mechanism operating in the adult. Taken together, the present findings suggest that GDNF acts endogenously as a target-derived physiological survival/maintenance factor for dopaminergic neurons.
Cyclodextrins in delivery systems: Applications (2010)

Cyclodextrins (CDs) are a family of cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic central cavity. CD molecules are relatively large with a number of hydrogen donors and acceptors and, thus in general, they do not permeate lipophilic membranes. In the pharmaceutical industry, CDs have mainly been used as complexing agents to increase aqueous solubility of poorly soluble drugs and to increase their bioavailability and stability. CDs are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current CD-based therapeutics is described and possible future applications are discussed. CD-containing polymers are reviewed and their use in drug delivery is presented. Of specific interest is the use of CD-containing polymers to provide unique capabilities for the delivery of nucleic acids. Studies in both humans and animals have shown that CDs can be used to improve drug delivery from almost any type of drug formulation. Currently, there are approximately 30 different pharmaceutical products worldwide containing drug/CD complexes in the market.
A high-protein diet is anti-steatotic and has no pro-inflammatory side effects in dyslipidaemic APOE2 knock-in mice (2014)

High-protein (HP) diets are effective anti-steatotic treatment options for patients with non-alcoholic fatty liver disease, but whether these diets also decrease steatosis in hyperlipidaemic conditions is not known. The aim of the present study was to determine the effects of a HP diet on hepatic steatosis and inflammation in hyperlipidaemic mice. Hyperlipidaemic male and female APOE2 knock-in (APOE2ki) mice were fed a semi-synthetic low-protein (LP) or HP diet in combination with a low-fat diet or a high-fat diet for 3 weeks. The HP diets reduced hepatic fat and cholesterol concentrations to 40-55 % of those induced by the corresponding LP diets and attenuated hepatic inflammation mildly. The VLDL-associated plasma cholesterol concentrations decreased to 60-80 %, but those of TAG increased 3-4-fold. APOE2-mediated restriction of fat import into the liver did not modify the effects of a HP diet previously observed in wild-type mice. Female APOE2ki mice exhibited a higher expression of lipogenic, cholesterol-synthesising, inflammatory and cell-stress genes than wild-type female or male APOE2ki mice, but a similar response to HP diets. Low Apob expression and unchanged plasma APOB100 concentrations suggest that HP diets increase the plasma concentrations of TAG by slowing their clearance. The decrease in plasma leptin and hepatic fat and glycogen concentrations and the increase in fatty acid-oxidising gene and phosphoenolpyruvate carboxykinase 1 protein expression suggest a HP diet-mediated increase in mitochondrial metabolism. In conclusion, a HP diet reduces hepatic lipid content in dyslipidaemic mice and lowers the activation status of inflammatory cells in the liver.
Vibration Reduction Using Multi-Hump Input Shapers (1997)

Input shaping is a method for reducing residual vibrations in computer-controlled machines. Vibration is eliminated by convolving an input shaper, which is a sequence of impulses, with a desired system command to produce a shaped input. The shaped input then becomes the command to the system. Requiring the vibration reduction to be robust to modeling errors and system nonlinearities is critical to the success of the shaping process on any real system, Input shapers can be made very insensitive to parameter uncertainty; however, increasing robustness usually increases system delays. A design process is presented that generates input shapers with insensitivity-to-time-delay ratios that are much larger than traditionally designed input shapers. The advantages of the new shapers are demonstrated with computer simulations and their performance is verified with experimental results from the MIT Middeck Active Control Experiment, which was performed on board the Space Shuttle Endeavor.
Interaction of Tobamovirus Movement Proteins with the Plant Cytoskeleton (1995)

The movement protein of tobacco mosaic tobamovirus and related viruses is essential for the cell-to-cell spread of infection and, in part, determines the host range of the virus. Movement protein (MP) was fused with the jellyfish green fluorescent protein (GFP), and a modified virus that contained this MP:GFP fusion protein retained infectivity. In protoplasts and leaf tissues, the MP:GFP fusion protein was detected as long filaments shortly after infection. Double-labeling fluorescence microscopy suggests that the MP interacts and coaligns with microtubules. The distribution of the MP is disrupted by treatments that disrupt microtubules, but not by cytochalasin B, which disrupts filamentous F-actin. Microtubules may target the MP to plasmodesmata, the intercellular channels that connect adjacent cells.
Overview of P-glycoprotein inhibitors: a rational outlook (2012)

P-glycoprotein (P-gp), a transmembrane permeability glycoprotein, is a member of ATP binding cassette (ABC) super family that functions specifically as a carrier mediated primary active efflux transporter. It is widely distributed throughout the body and has a diverse range of substrates. Several vital therapeutic agents are substrates to P-gp and their bioavailability is lowered or a resistance is induced because of the protein efflux. Hence P-gp inhibitors were explored for overcoming multidrug resistance and poor bioavailability problems of the therapeutic P-gp substrates. The sensitivity of drug moieties to P-gp and vice versa can be established by various experimental models in silico, in vitro and in vivo. Ever since the discovery of P-gp, the research plethora identified several chemical structures as P-gp inhibitors. The aim of this review was to emphasize on the discovery and development of newer, inert, non-toxic, and more efficient, specifically targeting P-gp inhibitors, like those among the natural herb extracts, pharmaceutical excipients and formulations, and other rational drug moieties. The applications of cellular and molecular biology knowledge, in silico designed structural databases, molecular modeling studies and quantitative structure-activity relationship (QSAR) analyses in the development of novel rational P-gp inhibitors have also been mentioned.
Binding characteristics of N-acetylglucosamine-specific lectin of the isolated chicken hepatocytes: similarities to mammalian hepatic galactose/N-acetylgalactosamine-specific lectin (1989)

Binding characteristics of N-acetylglucosamine- (GlcNAc) specific lectin on the chicken hepatocyte surface were probed by an inhibition assay using various sugars and glycosides as inhibitors. Results indicated that the binding area of the lectin is small, interacting only with GlcNAc residues whose 3- and 4-OH's are open. The combining site is probably of trough-type, since substitution with as large a group as monosaccharide is permitted on the C-6 side of GlcNAc, and on the C-1 side, the aglycon of GlcNAc can be very large (e.g., a glycoprotein). These binding characteristics are shared with the homologous mammalian lectin specific for galactose/N-acetylgalactosamine, suggesting that tertiary structure of the combining area of these two lectins is similar. This is understandable, since there is approximately 40% amino acid sequence identity in the carbohydrate recognition domain of these two lectins [Drickamer, K., Mannon, J. F., Binns, G., & Leung, J. O. (1984) J. Biol. Chem. 259, 770-778]. A series of glycosides, each containing two GlcNAc residues separated by different distances (from 0.8 to 4.7 nm), were synthesized. Inhibition assay with these and other cluster glycosides indicated that clustering of two or more GlcNAc residues increased the affinity toward the chicken lectin tremendously. Among the ligands containing two GlcNAc residues, the structure which allows a maximal inter-GlcNAc distance of 3.3 nm had the strongest affinity, its affinity increase over GlcNAc (monosaccharide) amounting to 100-fold. Longer distances slightly diminished the affinity, while shortening the distance caused substantial decrease in the affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthesis of New Deoxycholic Acid bis Thiocarbazones under Solvent-Free Conditions using Microwave Irradiation (2011)

A simple method for the synthesis of new deoxycholic acid bis thiocarbazones under solvent-free conditions using microwave irradiation has been developed. Its main advantages are short reaction times, good conversions and the environmentally friendly nature of the process. Their structures were characterised by 1 H NMR, IR, ESI-MS spectra and elemental analysis. The preliminary results indicate that some of these compounds possess inhibitory effects against Escherichia coli.
Low-complexity face-assisted video coding (2000)

This paper presents a novel face-assisted video coding scheme to enhance the visual quality of the face regions in video telephony applications. A skin-color based face detection and tracking scheme is proposed to locate the face regions in real-time. After classifying the macroblocks into the face and non-face regions, we present a dynamic distortion weighting adjustment (DDWA) scheme to drop the static non-face macroblocks, and the saved bits are used to compensate the face region by adjusting the distortion weighting of the face macroblocks. The quality of face regions will thus be enhanced. Moreover, the computation originally required for the skipped macroblocks can also be saved. The experimental results show that the proposed method can significantly improve the PSNR and the subjective quality of face regions, while the degradation introduced on the non-face areas is relatively insensitive to human perception. The proposed algorithm is fully compatible with the H.263 standard, and the low complexity feature makes it well suited to implement for real-time applications.
Excimer laser ablation of the human lens at 308 nm with a fiber delivery system (1989)

A 308 nm excimer laser has been used with a fiber delivery system to perform ablation of the human lens. Preliminary results demonstrate the system's ability to ablate lens nucleus and cortex selectively, preserving the anterior and posterior capsules. The total delivered energy necessary to ablate a human lens ranged from 35 to 63 joules. Laser tissue interaction and ablation rates were computed for the different components of the human lens (capsule, cortex, nucleus) for the operatively useful energy densities (fluences). Operative experience suggests that cortex and nucleus can be ablated while preserving the capsule if an adequate irrigation and aspiration system is developed. These results also suggest that this modality may be adequate for performing endocapsular cataract extraction. Laser tissue interactions were also computed at variable distances between the fiber tip and tissue. As this distance increased, the spread of the beam increased and a significant increase in energy was necessary to induce tissue ablation. This was due to the decrease in fluence with increasing distance to the target tissue and/or the absorption and scattering of the delivered energy within a short distance from the fiber tip by the ablated material. Evidence of a sonic effect was also present.
A Semicontinuous Prokaryotic Coupled Transcription/Translation System Using a Dialysis Membrane (1996)

This report describes a novel and simple cell-free protein synthesis system. In this paper, we prove that the short duration of protein synthesis in a conventional cell-free protein synthesis system of batch configuration can be attributed both to depletion of energy sources and deactivation of S30 extract by small-molecule byproducts produced during the protein synthesis. The reaction period of cell-free protein synthesis system could be extended through an operation of a continuous-flow cell-free protein synthesis system, which was originally developed by Spirin. However, inspite of the greatly extended reaction period, the final amount of cell-free produced protein was not significantly larger than that can be obtained from a batch system due to the reduced rate of protein synthesis. It was supposed that the reduced rate of protein synthesis in the continuous-flow system was attributed to leakage of translational components through the ultrafiltration membrane during the operation of the continuous-flow system. To solve such a problem of the continuous-flow system, we have developed and operated a novel reactor for cell-free protein synthesis. By use of this system, protein synthesis occurred for at least 14 h, yielding 1.2 mg/mL CAT protein. The present system is superior to the continuous-flow system as well as the conventional batch system in that it enables extremely high productivity without using any complex and hard-to-handle apparatus. As far as we know, the yield of cell-free protein synthesis given above is the best of the results reported to date.
Acylation of Lysine 860 Allows Tight Binding and Cytotoxicity ofBordetellaAdenylate Cyclase on CD11b-Expressing Cells (2005)

The Bordetella adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) forms cation-selective membrane channels and delivers into the cytosol of target cells an adenylate cyclase domain (AC) that catalyzes uncontrolled conversion of cellular ATP to cAMP. Both toxin activities were previously shown to depend on post-translational activation of proCyaA to CyaA by covalent palmitoylation of the internal Lys983 residue (K983). CyaA, however, harbors a second RTX acylation site at residue Lys860 (K860), and the role of K860 acylation in toxin activity is unclear. We produced in E. coli the CyaA-K860R and CyaA-K983R toxin variants having the Lys860 and Lys983 acylation sites individually ablated by arginine substitutions. When examined for capacity to form membrane channels and to penetrate sheep erythrocytes, the CyaA-K860R acylated on Lys983 was about 1 order of magnitude more active than CyaA-K983R acylated on Lys860, although, in comparison to intact CyaA, both monoacylated constructs exhibited markedly reduced activities in erythrocytes. Channels formed in lipid bilayers by CyaA-K983R were importantly less selective for cations than channels formed by CyaA-K860R, intact CyaA, or proCyaA, showing that, independent of its acylation status, the Lys983 residue may play a role in toxin structures that determine the distribution of charged residues at the entry or inside of the CyaA channel. While necessary for activity on erythrocytes, acylation of Lys983 was also sufficient for the full activity of CyaA on CD11b+ J774A.1 monocytes. In turn, acylation of Lys860 alone did not permit toxin activity on erythrocytes, while it fully supported the high-affinity binding of CyaA-K983R to the toxin receptor CD11b/CD18 and conferred on CyaA-K983R a reduced but substantial capacity to penetrate and kill the CD11b+ cells. This is the first evidence that acylation of Lys860 may play a role in the biological activity of CyaA, even if redundant to the acylation of Lys983.
Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas (2011)

NRP1 (neuropilin-1) is a co-receptor for members of the VEGF (vascular endothelial growth factor) family in endothelial cells, but is increasingly implicated in signalling induced by other growth factors. NRP1 is expressed in VSMCs (vascular smooth muscle cells), but its function and the mechanisms involved are poorly understood. The present study aimed to determine the role of NRP1 in the migratory response of HCASMCs (human coronary artery smooth muscle cells) to PDGF (platelet-derived growth factor), and to identify the signalling mechanisms involved. NRP1 is highly expressed in HAoSMCs (human aortic smooth muscle cells) and HCASMCs, and modified in VSMCs by CS (chondroitin sulfate)-rich O-linked glycosylation at Ser612. HCASMC migration induced by PDGF-BB and PDGF-AA was inhibited by NRP1 siRNA (small interfering RNA), and by adenoviral overexpression of an NRP1 mutant lacking the intracellular domain (Ad.NRP1ΔC). NRP1 co-immunoprecipitated with PDGFRα (PDGF receptor α), and immunofluorescent staining indicated that NRP1 and PDGFRα co-localized in VSMCs. NRP1 siRNA also inhibited PDGF-induced PDGFRα activation. NRP1-specific siRNA, Ad.NRP1ΔC and removal of CS glycans using chondroitinase all inhibited PDGF-BB and -AA stimulation of tyrosine phosphorylation of the adapter protein, p130Cas (Cas is Crk-associated substrate), with little effect on other major signalling pathways, and p130Cas knockdown inhibited HCASMC migration. Chemotaxis and p130Cas phosphorylation induced by PDGF were inhibited by chondroitinase, and, additionally, adenoviral expression of a non-glycosylatable NRP1S612A mutant inhibited chemotaxis, but not p130Cas phosphorylation. These results indicate a role for NRP1 and NRP1 glycosylation in mediating PDGF-induced VSMC migration, possibly by acting as a co-receptor for PDGFRα and via selective mobilization of a novel p130Cas tyrosine phosphorylation pathway.
Oxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite Catalyzed by TEMPO and Bleach (1999)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTOxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite Catalyzed by TEMPO and BleachMangzhu Zhao, Jing Li, Eiichi Mano, Zhiguo Song, David M. Tschaen, Edward J. J. Grabowski, and Paul J. ReiderView Author Information Process Research Department, Merck Research Laboratories, Merck & Co. Inc., P.O. Box 2000, Rahway, New Jersey 07065 Cite this: J. Org. Chem. 1999, 64, 7, 2564–2566Publication Date (Web):March 18, 1999Publication History Received26 October 1998Published online18 March 1999Published inissue 1 April 1999https://pubs.acs.org/doi/10.1021/jo982143yhttps://doi.org/10.1021/jo982143ybrief-reportACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views20926Altmetric-Citations397LEARN 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:Alcohols,Aromatic compounds,Halogenation,Organic acids,Oxidation Get e-Alerts
Object-oriented concepts, databases, and applications (1989)

A growing interest in the object-oriented programming paradigm prompted the editors to compile a wide-ranging introduction to the subject, beginning with basic concepts and then covering a variety of applications in databases and other areas. Most of the contributions, by leading figures in the field, were written specifically for this volume. Topics include object-oriented programming languages, application systems, operational object-oriented database systems,architectural issues, and directions in future research and development. ACM Press Frontier Series. 0201144107B04062001
Practice enables successful learning under minimal guidance. (2009)

Two experiments were conducted, contrasting a minimally guided discovery condition with a variety of instructional conditions. College students interacted with a computer-based tutor that presented algebra-like problems in a novel graphical representation. Although the tutor provided no instruction in a discovery condition, it constrained the possible actions sufficiently that students could always discover the algebraic transformations they needed to learn. In Experiment 1, with ample practice for each new transformation, students performed better in the discovery condition than any instructional condition. In Experiment 2, with only a little practice for each transformation, students performed worst in the discovery condition. The authors suggest that the high levels of practice in the 1st experiment made students more efficient at discovering the algebraic transformations. When the cognitive demands were manageable, the discovery students may have more often encoded the algebraic transformations in mathematically correct ways.
Functional and structural conservation in the mechanosensitive channel MscL implicates elements crucial for mechanosensation (1998)

mscL encodes a channel in Escherichia coli that is opened by membrane stretch force, probably serving as an osmotic gauge. Sequences more or less similar to mscL are found in other bacteria, but the degree of conserved function has been unclear. We subcloned and expressed these putative homologues in E. coli and examined their products under patch clamp. Here, we show that each indeed encodes a conserved mechanosensitive channel activity, consistent with the interpretation that this is an important and primary function of the protein in a wide range of bacteria. Although similar, channels of different bacteria differ in kinetics and their degree of mechanosensitivity. Comparison of the primary sequence of these proteins reveals two highly conserved regions, corresponding to domains previously shown to be important for the function of the wild-type E. coli channel, and a C-terminal region that is not conserved in all species. This structural conservation is providing insight into regions of this molecule that are vital to its role as a mechanosensitive channel and may have broader implications for the understanding of other mechanosensitive systems.