gebhart/patrepeval huggingface dataset:
Prolonged Incubation with Laquinimod Protects Hippocampal Cells from Oxidative Stress (P02.110) (2012)

Objective: To evaluate the antioxidant potential of Laquinimod, a novel oral therapeutic for the treatment of Multiple Sclerosis (MS). Background MS is an inflammatory autoimmune disorder, where chronic disability is due to axonal and neuronal degeneration, which is not accessible to conventional therapy and linked to oxidative stress. Laquinimod is an orally administered CNS-active immunomodulator. Phase III data in RRMS patients showed beneficial effects of laquinimod on clinical disease activity as evidenced by slowing the progression of disability, reducing the rate of MRI-measured brain volume loss and reducing relapse rates, all coupled with a favorable safety and tolerability profile. Design/Methods: We investigated the role of laquinimod in oxidative stress using hippocampal HT22 cells. In these cells, extracellular glutamate blocks cystine import via the glutamate/cystine-antiporter system Χc. Lack of intracellular cystine leads to glutathione depletion and cell death due to oxidative stress. Protection in this model was previously shown to be mediated by the transcription factors ATF4, CREB, NRF2 or SRF. We measured cell survival, concentration and time dependence, total cellular glutathione content, and the induction of antioxidant proteins by quantitative real-time PCR and transcriptional activation by dual-luciferase experiments. Results: Laquinimod robustly protected against glutamate toxicity, inhibition of γ-glutamylsynthetase, and direct oxidative stress induced by hydrogen peroxide without elevating basal intracellular glutathione levels. Protection was time-dependent and took seven days to develop. We observed a relevant effect on the expression of glutamate cysteine ligase and xCT, the functional unit of system Χc. Conclusions: Laquinimod protects hippocampal HT22 cells from oxidative stress. This protection takes seven days to develop, which hints to mechanism involving changes in gene transcription not mediated by NRF2. These results suggest transcriptional activation by other transcription factors, which are currently investigated by dual luciferase experiments using promoters of glutamate cysteine ligase and xCT. Supported by: TEVA. Disclosure: Dr. Methner has nothing to disclose. Dr. Albrecht has received research support from Novartis. Dr. Bouchachia has nothing to disclose. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Genzyme Corporation, Merck Serono, Novartis, Sanofi-Aventis and Teva as a speaker and/or consultant.
Quantitative Microplate Assay for Studying Mesenchymal Stromal Cell-Induced Neuropoiesis (2013)

Transplanting mesenchymal stromal cells (MSCs) or their derivatives in a neurodegenerative environment is believed to be beneficial because of the trophic support, migratory guidance, and neurogenic stimuli they provide. There is a growing need for in vitro models of mesenchymal-neural cell interactions to enable identification of mediators of the MSC activity and quantitative assessment of neuropoietic potency of MSC preparations. Here, we characterize a microplate-format coculture system in which primary embryonic rat cortex cells are directly cocultured with human MSCs on cell-derived extracellular matrix (ECM) in the absence of exogenous growth factors. In this system, expression levels of the rat neural stem/early progenitor marker nestin, as well as neuronal and astrocytic markers, directly depended on MSC dose, whereas an oligodendrogenic marker exhibited a biphasic MSC-dose response, as measured using species-specific quantitative reverse transcription-polymerase chain reaction in total cell lysates and confirmed using immunostaining. Both neural cell proliferation and differentiation contributed to the MSC-mediated neuropoiesis. ECM's heparan sulfate proteoglycans were essential for the growth of the nestin-positive cell population. Neutralization studies showed that MSC-derived fibroblast growth factor 2 was a major and diffusible inducer of rat nestin, whereas MSC-derived bone morphogenetic proteins (BMPs), particularly, BMP4, were astrogenesis mediators, predominantly acting in a coculture setting. This system enables analysis of multifactorial MSC-neural cell interactions and can be used for elucidating the neuropoietic potency of MSCs and their derivative preparations.
Direct Synthesis of Polymer Nanocapsules with a Noncovalently Tailorable Surface (2007)

Hollow out your pumpkin: The direct synthesis of approximately 100-nm-diameter polymer nanocapsules was carried out in the absence of preorganized structures or templates. The method appears to be applicable to any monomer that has a flat core and multiple polymerizable groups at the periphery (see picture). The surface properties of the polymer shell, which comprises cucurbituril, can be easily tailored through host–guest chemistry. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z604526_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Acquired Immunodeficiency Syndrome (AIDS) Dementia Complex (1989)

The acquired immunodeficiency syndrome (AIDS) dementia complex is a frequent and devastating complication of infection with human immunodeficiency virus-type 1 (HIV-1). Features of the AIDS dementia complex include decreased memory, the inability to concentrate, apathy, and psychomotor retardation. Typical neuropathologic findings include gliosis, focal necrosis of neurons, perivascular inflammation, formation of microglial nodules, multinucleated giant cells, and demyelination. That HIV-1 is the direct cause of this neurologic syndrome is strongly supported by the available evidence. In addition, several studies have identified the monocyte-macrophage as the predominant cell type in the brain infected with HIV-1. However, the mechanisms by which the infected monocytes-macrophages mediate neurologic dysfunction and destruction have not been elucidated.
Protection of thyroid cancer cells by complement-regulatory factors (1994)

The present study confirmed the presence of complement activation with subsequent deposition of C3d and C5b-9 complexes in thyroid carcinomas. It also indicated that thyroid carcinoma cells are protected from cell lysis because of complement activation in multiple phases by complete coverage of the entire cell membrane surface with complement-regulatory factors. These findings were similar to those found in nonneoplastic thyroid follicular cells.
Fibre optic microarrays (2009)

This tutorial review describes how fibre optic microarrays can be used to create a variety of sensing and measurement systems. This review covers the basics of optical fibres and arrays, the different microarray architectures, and describes a multitude of applications. Such arrays enable multiplexed sensing for a variety of analytes including nucleic acids, vapours, and biomolecules. Polymer-coated fibre arrays can be used for measuring microscopic chemical phenomena, such as corrosion and localized release of biochemicals from cells. In addition, these microarrays can serve as a substrate for fundamental studies of single molecules and single cells. The review covers topics of interest to chemists, biologists, materials scientists, and engineers.
Telophase enucleation: An improved method to prepare recipient cytoplasts for use in bovine nuclear transfer (1998)

The enucleation of oocytes to be used as host cytoplasts for embryo reconstruction by nuclear transfer is an important limiting step when cloning mammals. We propose an enucleation technique based on the removal of chromatin after oocyte activation, at the telophase stage, by aspirating the second polar body and surrounding cytoplasm. In a preliminary experiment to determine an optimal activation protocol, oocytes were matured for 26 and 30 hr and exposed for 5 min to 7% ethanol and/or for 3 hr at either 25 or 4 degrees C. Relative to most activation treatments tested, oocytes matured for 30 hr and exposed to ethanol alone showed highest activation rates, as determined by low levels of H1 kinase activity within 90 min from exposure and high pronuclear formation (82%) after 12 hr of culture. No synergistic effect on activation rates was observed when oocytes also were exposed to reduced temperature after ethanol treatment. Microsurgical removal of the telophase-stage chromatin in a small volume of cytoplasm adjacent to the second polar body was significantly more effective in enucleating than aspiration of a larger cytoplasm volume surrounding the first polar body of metaphase-arrested oocytes (98% versus 59%; P < 0.01). Moreover, compared with a nuclear transfer protocol based on enucleation of metaphase-arrested oocytes followed by aging and cooling, more (38% versus 16%; P < 0.001) and better-quality blastocytes (126 versus 84 nuclei per blastocyst; P < 0.02) were obtained from embryos reconstructed using the telophase procedure. Higher development potential of embryos reconstructed by the telophase procedure may be attributed to (1) the selection of oocytes that activate and respond by extruding the second polar body, (2) avoiding the use of DNA dyes and ultraviolet irradiation, and (3) the limited removal of cytoplasm during enucleation. The ease with which telophase enucleation can be performed is likely to render this technique widely useful for research and practice on mammalian cloning.
Design and Fabrication of Scanning Near-Field Microwave Probes Compatible With Atomic Force Microscopy to Image Embedded Nanostructures (2004)

Design, fabrication, and characterization of near-field microwave scanning probes compatible with an atomic force microscope (AFM) for imaging of embedded nanostructures are discussed. The microwave probe discussed here bridges the frequency gap between the existing local probe microscopy systems, and enables localized microwave spectroscopy and imaging of molecules and nanostructures. The probe consists of a coaxially shielded heavily doped silicon tip, and an aluminum (Al) coplanar waveguide. The coaxial tip structure was formed by a thick photoresist and plasma etching process, enabling the silicon apex to protrude through a well-defined aperture in the Al layer. Using this technique, probes with 10-/spl mu/m-high coaxial tips of 5-nm apex radius and 500-nm aperture radius were realized. The aperture confines the electromagnetic fields in the exposed tip region, allowing microwave measurements with high spatial resolution. The mechanical and electrical characterizations of the microwave probes were performed to ensure their compliance with the requirement of an AFM, as well as that of the microwave measurements. Finally, simultaneous AFM and microwave imaging of standard AFM samples with grid structures was performed for the first time. The lateral spatial resolution of the microwave scans was approximately 50 nm at 2.8 GHz, compared to 100 nm for the AFM scans. The ability of the microwave signal to penetrate inside the sample opens new possibilities in hyperspectral and multimodal imaging of nanostructures. Correlations between AFM images and the microwave images enable proper registration and referencing of the microwave properties to landmarks in the topographic AFM images.
Evidence for a prolonged role of alpha sub 4 integrin throughout active experimental allergic encephalomyelitis (1996)

The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.
Ins and Outs of Major Facilitator Superfamily Antiporters (2008)

The major facilitator superfamily (MFS) represents the largest group of secondary active membrane transporters, and its members transport a diverse range of substrates. Recent work shows that MFS antiporters, and perhaps all members of the MFS, share the same three-dimensional structure, consisting of two domains that surround a substrate translocation pore. The advent of crystal structures of three MFS antiporters sheds light on their fundamental mechanism; they operate via a single binding site, alternating-access mechanism that involves a rocker-switch type movement of the two halves of the protein. In the sn-glycerol-3-phosphate transporter (GlpT) from Escherichia coli, the substrate-binding site is formed by several charged residues and a histidine that can be protonated. Salt-bridge formation and breakage are involved in the conformational changes of the protein during transport. In this review, we attempt to give an account of a set of mechanistic principles that characterize all MFS antiporters.
A Dual-Readout F 2 Assay That Combines Fluorescence Resonance Energy Transfer and Fluorescence Polarization for Monitoring Bimolecular Interactions (2011)

Förster (fluorescence) resonance energy transfer (FRET) and fluorescence polarization (FP) are widely used technologies for monitoring bimolecular interactions and have been extensively used in high-throughput screening (HTS) for probe and drug discovery. Despite their popularity in HTS, it has been recognized that different assay technologies may generate different hit lists for the same biochemical interaction. Due to the high cost of large-scale HTS campaigns, one has to make a critical choice to employee one assay platform for a particular HTS. Here we report the design and development of a dual-readout HTS assay that combines two assay technologies into one system using the Mcl-1 and Noxa BH3 peptide interaction as a model system. In this system, both FP and FRET signals were simultaneously monitored from one reaction, which is termed "Dual-Readout F(2) assay" with F(2) for FP and FRET. This dual-readout technology has been optimized in a 1,536-well ultra-HTS format for the discovery of Mcl-1 protein inhibitors and achieved a robust performance. This F(2) assay was further validated by screening a library of 102,255 compounds. As two assay platforms are utilized for the same target simultaneously, hit information is enriched without increasing the screening cost. This strategy can be generally extended to other FP-based assays and is expected to enrich primary HTS information and enhance the hit quality of HTS campaigns.
Three-dimensional crystallization of membrane proteins (1988)

As recently as 10 years ago, the prospect of solving the structure of any membrane protein by X-ray crystallography seemed remote. Since then, the threedimensional (3-D) structures of two membrane protein complexes, the bacterial photosynthetic reaction centres of Rhodopseudomonas viridis (Deisenhofer et al. 1984, 1985) and of Rhodobacter sphaeroides (Allen et al. 1986, 1987 a, 6 ; Chang et al. 1986) have been determined at high resolution. This astonishing progress would not have been possible without the pioneering work of Michel and Garavito who first succeeded in growing 3-D crystals of the membrane proteins bacteriorhodopsin (Michel &amp; Oesterhelt, 1980) and matrix porin (Garavito &amp; Rosenbusch, 1980). X-ray crystallography is still the only routine method for determining the 3-D structures of biological macromolecules at high resolution and well-ordered 3-D crystals of sufficient size are the essential prerequisite.
A randomized controlled trial of recombinant interferon-beta 1a in Guillain-Barre syndrome (2003)

The authors recruited 19 nonambulant patients with Guillain-Barré syndrome into a pilot, double-blind, randomized, placebo-controlled safety trial of interferon beta 1a (IFN[beta]-1a) (Rebif). Participants received IFN[beta]-1a or placebo subcutaneously three times weekly, 22 microg for the first week and then 44 microg for up to 24 weeks, in addition to IV immunoglobulin (IVIg). IFN[beta] did not have any unexpected interaction with IVIg and there was no significant difference in rate of improvement.
Simplex crossover and linkage identification: single-stage evolution vs. multi-stage evolution (2003)

Previous studies have proposed simplex crossover for real-coded genetic algorithms (GAs). In this paper, we propose two types of linkage identification for simplex crossover: the linkage identification with single-stage evolution (LISS) and linkage identification with multi-stage evolution (LIMS); and a comparative study is performed. Results show that the LIMS has a more stable performance than LISS.
Collaborative filtering with privacy (2005)

Server-based collaborative filtering systems have been very successful in e-commerce and in direct recommendation applications. In future, they have many potential applications in ubiquitous computing settings. But today's schemes have problems such as loss of privacy, favoring retail monopolies, and with hampering diffusion of innovations. We propose an alternative model in which users control all of their log data. We describe an algorithm whereby a community of users can compute a public "aggregate" of their data that does not expose individual users' data. The aggregate allows personalized recommendations to be computed by members of the community, or by outsiders. The numerical algorithm is fast, robust and accurate. Our method reduces the collaborative filtering task to an iterative calculation of the aggregate requiring only addition of vectors of user data. Then we use homomorphic encryption to allow sums of encrypted vectors to be computed and decrypted without exposing individual data. We give verification schemes for all parties in the computation. Our system can be implemented with untrusted servers, or with additional infrastructure, as a fully peer-to-peer (P2P) system.
Lens Opacity Meter: A New Instrument to Quantify Lens Opacity (1987)

The lens opacity meter, a new instrument for quantifying the lens opacity, is described. The basic concept is the measurement of stray light produced by the lens. The measurement can be performed without dilating the pupil. A modulation of the light source renders the measurement insensitive to the surrounding light. The handling of the instrument is very simple. It is mounted on a slitlamp-like table. After adjusting the instrument to the eye, the measurement is initiated by depressing a console button.
Leucine biosynthesis in Saccharomyces cerevisiae. Purification and characterization of beta-isopropylmalate dehydrogenase. (1980)

I-Isopropylmalate dehydrogenase (EC 1.1.1.85)from Saccharomyces cerevisiae strain SK103 was purified 1210-fold to a purity of about 97%.The enzyme, which is the LEU2 gene product, contains one type of subunit (Mr -45,000) and exists in a monomer-dimer equilibrium.It is cold labile.Cold lability is most pronounced in crude preparations and at pH values below neutrality.Purified enzyme is quite labile at all temperature and pH values tested.Protection of purified enzyme against dilution inactivation at pH 8.3 and 23°C is provided by glycerol or by Mn2+ plus either dithiothreitol, P-isopropylmalate, or a-ketoisocaproate.Partially inactivated enzyme can be reactivated by dithiothreitol plus Mn2+, but not by P-isopropylmalate plus Mn2+, suggesting that this inactivation is at least in part due to the oxidation of essential sulfhydryl groups.The Michaelis constants for both /I-isopropylmalate and NAD' are enzyme concentration-dependent.Under the conditions employed, the apparent K,,, values range from 2.3 X M to 4.2 X M for P-isopropylmalate and from 5.4 X lod5 M to 1.5 x M for NAD'.The enzyme requires divalent cations for full activity; Mn2+ and Cd2+ are most effective.A comparison of the yeast P-isopropylmalate dehydrogenase with that from Salmonella typhimurium shows that the most striking dif- ferences are the subunit molecular weight (45,000 uer- sus 35,000) and the cold sensitivity (only the yeast enzyme is cold labile).
Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. (1993)

Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.
Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice (2011)

Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.