gebhart/patrepeval huggingface dataset:
Poloxamer 188 inhibition of ischemia/reperfusion injury: evidence for a novel anti-adhesive mechanism. (2010)

Poloxamer 188 (P188) is a nonionic block copolymer surfactant that has rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities. Several mechanisms have previously been proposed, but none explain all of the observed effects. In this study, superior mesenteric artery occlusion (SMAO) was employed as a clinically relevant model of ischemia/reperfusion. The superior mesenteric artery of rats was clamped for one hr and and followed by reperfusion with P188 or saline for five hr, after which tissues were harvested for expression microarray, histologic, enzymatic, and western blot analyses. The results demonstrated that P188 significantly inhibits the entire spectrum of inflammatory, coagulation, and apoptotic responses produced by SMAO. This supports the existence of a novel mechanism that recognizes two types of adhesive interactions. The first, specific receptor-ligand adhesion, governs interactions between cells and molecules and is unaffected by P188. P188 affects only the second type, hydrophobic adhesion, which is responsible for the integrity of membranes and conformation of proteins. Hydrophobic interactions are non-specific because they derive from repulsion of water rather than from affinity of molecules for one another. Ischemic membranes develop defects that expose underlying hydrophobic structures and trigger multiple deleterious responses. Fat emboli and hydrophobic proteins such as fibrin produced by the injury further compromise the microcirculation. The unique structure of P188 facilitates its rapid, but gentle, binding to any exposed hydrophobic domain, restoring normal non-adhesive surfaces and thereby preventing activation of the entire spectrum of deleterious reactions.
Using Flow to Switch the Valency of Bacterial Capture on Engineered Surfaces Containing Immobilized Nanoparticles (2012)

Toward an understanding of nanoparticle-bacterial interactions and the development of sensors and other substrates for controlled bacterial adhesion, this article describes the influence of flow on the initial stages of bacterial capture (Staphylococcus aureus) on surfaces containing cationic nanoparticles. A PEG (poly(ethylene glycol)) brush on the surface around the nanoparticles sterically repels the bacteria. Variations in ionic strength tune the Debye length from 1 to 4 nm, increasing the strength and range of the nanoparticle attractions toward the bacteria. At relatively high ionic strengths (physiological conditions), bacterial capture requires several nanoparticle-bacterial contacts, termed "multivalent capture". At low ionic strength and gentle wall shear rates (on the order of 10 s(-1)), individual bacteria can be captured and held by single surface-immobilized nanoparticles. Increasing the flow rate to 50 s(-1) causes a shift from monovalent to divalent capture. A comparison of experimental capture efficiencies with statistically determined capture probabilities reveals the initial area of bacteria-surface interaction, here about 50 nm in diameter for a Debye length κ(-1) of 4 nm. Additionally, for κ(-1) = 4 nm, the net per nanoparticle binding energies are strong but highly shear-sensitive, as is the case for biological ligand-receptor interactions. Although these results have been obtained for a specific system, they represent a regime of behavior that could be achieved with different bacteria and different materials, presenting an opportunity for further tuning of selective interactions. These finding suggest the use of surface elements to manipulate individual bacteria and nonfouling designs with precise but finite bacterial interactions.
Equilibrium and non-equilibrium microfireball behaviour in light-ion fusion systems (1984)

Light-ion fusion reactors and high-yield target testing facilities will have a gas-filled reaction vessel.The target microexplosion will create a microfireball in this gas.The behaviour of this microfireball as it propagates and reflects from the reaction vessel wall is critical to the design of the vessel.The type of gas and the modelling assumptions used for analysis can significantly affect the prediction of this behaviour.The effects of two-temperature and multifrequency radiative transfer models are investigated for nitrogen and argon gases.The isothermal sphere model and the target X-ray attenuation model for microfireball creation are compared.The computational results are related to the analytic strongshock theory.
Tracing Cross Border Web Tracking (2018)

A tracking flow is a flow between an end user and a Web tracking service. We develop an extensive measurement methodology for quantifying at scale the amount of tracking flows that cross data protection borders, be it national or international, such as the EU28 border within which the General Data Protection Regulation (GDPR) applies. Our methodology uses a browser extension to fully render advertising and tracking code, various lists and heuristics to extract well known trackers, passive DNS replication to get all the IP ranges of trackers, and state-of-the art geolocation. We employ our methodology on a dataset from 350 real users of the browser extension over a period of more than four months, and then generalize our results by analyzing billions of web tracking flows from more than 60 million broadband and mobile users from 4 large European ISPs. We show that the majority of tracking flows cross national borders in Europe but, unlike popular belief, are pretty well confined within the larger GDPR jurisdiction. Simple DNS redirection and PoP mirroring can increase national confinement while sealing almost all tracking flows within Europe. Last, we show that cross boarder tracking is prevalent even in sensitive and hence protected data categories and groups including health, sexual orientation, minors, and others.
Less Mortality but More Relapses in Experimental Allergic Encephalomyelitis in CD8 -/- Mice (1992)

Mice lacking in CD8 were generated from homologous recombination in embryonal stem cells at the CD8 locus and bred with the experimental allergic encephalomyelitis (EAE)-susceptible PL/JH-2u through four backcross generations to investigate the role of CD8+ T cells in this model of multiple sclerosis. The disease onset and susceptibility were similar to those of wild-type mice. However, the mutant mice had a milder acute EAE, reflected by fewer deaths, but more chronic EAE, reflected by a higher frequency of relapse. This suggests that CD8+ T lymphocytes may participate as both effectors and regulators in this animal model.
( R )-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible (2013)

Mutations in IDH1 and IDH2, the genes coding for isocitrate dehydrogenases 1 and 2, are common in several human cancers, including leukemias, and result in overproduction of the (R)-enantiomer of 2-hydroxyglutarate [(R)-2HG]. Elucidation of the role of IDH mutations and (R)-2HG in leukemogenesis has been hampered by a lack of appropriate cell-based models. Here, we show that a canonical IDH1 mutant, IDH1 R132H, promotes cytokine independence and blocks differentiation in hematopoietic cells. These effects can be recapitulated by (R)-2HG, but not (S)-2HG, despite the fact that (S)-2HG more potently inhibits enzymes, such as the 5'-methylcytosine hydroxylase TET2, that have previously been linked to the pathogenesis of IDH mutant tumors. We provide evidence that this paradox relates to the ability of (S)-2HG, but not (R)-2HG, to inhibit the EglN prolyl hydroxylases. Additionally, we show that transformation by (R)-2HG is reversible.
Measles virus-specific human T cell clones. Characterization of specificity and function of CD4+ helper/cytotoxic and CD8+ cytotoxic T cell clones. (1989)

PBMC from healthy adult individuals seropositive for measles virus (MV) were tested for their capacity to proliferate to UV-inactivated MV (UV-MV) or to autologous MV-infected EBV-transformed B cell lines (EBV-BC). MV-specific T cell responses were observed in 11 of 15 donors tested (stimulation index greater than 2), when optimal doses of UV-MV were used in proliferative assays. T cell clones were generated from PBMC of three donors responding to MV, by using either UV-MV or MV-infected autologous EBV-BC as APC. Stimulation with UV-MV generated exclusively CD3+ CD4+ CD8- MV-specific T cells, whereas after stimulation of PBMC with MV-infected EBV-BC, both CD3+ CD4+ CD8- and CD3+ CD4- CD8+ MV-specific T cell clones were obtained. Of 19 CD4+ T cell clones tested so far, 7 clones reacted specifically with purified fusion protein and 1 with purified hemagglutinin protein. Seven clones proliferated in response to the internal proteins of MV. Three clones reacted to whole virus but not to one of the purified proteins, whereas one clone seemed to recognize more than one polypeptide. Some of the T cell clones, generated from in vitro stimulation of PBMC with UV-MV, failed to recognize MV Ag when MV-infected EBV-BC were used as APC instead of UV-MV and PBMC. CD3+ CD4+ CD8- T cell clones recognized MV in association with HLA class II Ag (HLA-DQ or -DR), and most of them displayed CTL activity to autologous MV-infected EBV-BC. All CD4+ HLA class II-restricted CTL clones thus far tested were capable of assisting B lymphocytes for the production of MV-specific antibody. The CD4- CD8+ T cell clone MARO 1 recognized MV in association with HLA class I molecules and displayed cytotoxic activity toward MV-infected EBV-BC.
Transcriptional activity and nucleolar ultrastructure of embryonic rabbit nuclei after transplantation to enucleated oocytes (1996)

Changes in the level of transcriptional activity in 32-cell stage morula nuclei were studied after blastomere electrofusion to enucleated oocytes. Nuclear transplant recipients were pulse labelled with 3H-uridine during cultivation in vitro, embryos were then fixed and processed for autoradiography and electron microscopy. Transcriptional activity substantially decreased after 4.5 hr and was completely inhibited at last 15 hr after fusion. Transcription resumed thereafter in two-cell stage embryos and could be detected in both nuclei from 70% of the embryos analyzed. Transcription activity rapidly increased at the eight 16-cell stages, reaching the level typical for 32-cell stage nuclei used for the transfer. Changes in nucleolar ultrastructure after the nuclear transfer reflected the inhibition and subsequent reactivation of rRNA transcription. Nucleoli of 32-cell embryos had a typical structure of active nucleoli; many fibrillar centers surrounded and interconnected by threads of the dense fibrillar component and embedded in the granular component. Six hours following nuclear transplantation, these nucleoli underwent drastic changes including loss of granular material, collapse of nucleolar structure, and segregation of nucleolar components. Following the first cleavage, segregated fibrillar components of nucleoli manifested a complete inhibition of nucleolar transcription. Ribosomal RNA transcription was restored at the eight-cell stage and the sequence of ultrastructural changes was similar to that of the normal development. However, at the 32-cell stage, excessive extrusion of pre-ribosomal particles in the cytoplasm occurred, suggesting a possible alteration in regulating mechanisms of ribosome delivery. These results show that after fusion with enucleated metaphase II cytoplasm and subsequent activation, transcription is inhibited in donor embryonic nuclei and progressively increases again during cleavage; almost as in normal embryos. Migration of ribosomes into cytoplasm appears more intense in 32-cell stage reconstituted embryos but this does not seem to inhibit blastocyst building.
Transcriptional activation and nuclear targeting signals of the human androgen receptor (2021)

The androgen receptor (AR) is a signal-transducing protein required for sexual differentiation, development, and expression of the male phenotype. A series of human AR deletion mutants were created either by site-directed mutagenesis using restriction enzyme digestion, the polymerase chain reaction, or, for a series of unidirectional NH2-terminal deletions, exonuclease III digestion. Receptor mutants were expressed in monkey kidney COS cells as truncated AR proteins between 20 and 107 kDa as revealed on immunoblots, where wild type AR was a doublet of 114 and 108 kDa. Subcellular localization by immunocytochemical staining demonstrated androgen-dependent nuclear uptake of AR from a perinuclear region of the cytoplasm. A nuclear targeting signal similar in sequence and position to the glucocorticoid receptor and homologous to the SV40 large T antigen was required for androgen-induced nuclear uptake of wild type AR. AR mutants lacking the NH2-terminal and/or steroid binding domains were constitutively nuclear with reduced transcriptional activity. Transcriptional activation by wild type AR was androgen-dependent in cotransfection studies of CV1 cells using the chloramphenicol acetyltransferase reporter gene linked to the mouse mammary tumor virus promoter. Deletion mutagenesis revealed within the NH2-terminal region a domain required for full transcriptional activity and within the steroid binding domain, an inhibitory function, deletion of which yielded a constitutively active receptor. Inhibition of wild type AR by coexpression with an inactive NH2-terminal fragment suggested competition for nuclear factors required for transcriptional regulation. These studies demonstrate a concerted interplay among the domains of the AR protein in regulating gene transcription.
<title>Segmentation of frames in a video sequence using motion and other attributes</title> (1995)

Motion-compensated video coders typically segment a scene into arbitrary tiles, resulting in a compressed bitstream which is not physically or semantically related to the scene structure. This paper presents a method for segmenting video frames and coding motion of regions, where the regions are defined in terms of a number of different properties. The goal is a video coder which gives good compression while identifying coherent regions in a manner useful for both human users and automated scene-understanding processes. Both a supervised and an unsupervised clustering algorithm are used to segment an image sequence; both algorithms make use of multiple features including motion, texture, position, and color. By utilizing both the structure and motion information, we preserve the semantic/structural content of the different regions, and simultaneously remove the redundancy (in successive frames) by describing the motion information in each region with a six-parameter affine model. In the supervised clustering algorithm, the first frame is manually segmented and used as training data. The classification of subsequent frames is done automatically, by using a MAP estimate, and modeling the n-dimensional feature-space as jointly Gaussian. The unsupervised algorithm is an iterative process that reassigns the classification of each point to the region corresponding to the nearest mean among each region of the segmentation from the previous iteration. In both algorithms, the distance and/or the mean is an n-dimensional measurement, n being the number of features used.
A Liquid Chromatography-Mass Spectrometry-Based Metabolome Database for Tomato (2006)

For the description of the metabolome of an organism, the development of common metabolite databases is of utmost importance. Here we present the Metabolome Tomato Database (MoTo DB), a metabolite database dedicated to liquid chromatography-mass spectrometry (LC-MS)- based metabolomics of tomato fruit (Solanum lycopersicum). A reproducible analytical approach consisting of reversed-phase LC coupled to quadrupole time-of-flight MS and photodiode array detection (PDA) was developed for large-scale detection and identification of mainly semipolar metabolites in plants and for the incorporation of the tomato fruit metabolite data into the MoTo DB. Chromatograms were processed using software tools for mass signal extraction and alignment, and intensity-dependent accurate mass calculation. The detected masses were assigned by matching their accurate mass signals with tomato compounds reported in literature and complemented, as much as possible, by PDA and MS/MS information, as well as by using reference compounds. Several novel compounds not previously reported for tomato fruit were identified in this manner and added to the database. The MoTo DB is available at http://appliedbioinformatics.wur.nl and contains all information so far assembled using this LC-PDA-quadrupole time-of-flight MS platform, including retention times, calculated accurate masses, PDA spectra, MS/MS fragments, and literature references. Unbiased metabolic profiling and comparison of peel and flesh tissues from tomato fruits validated the applicability of the MoTo DB, revealing that all flavonoids and alpha-tomatine were specifically present in the peel, while several other alkaloids and some particular phenylpropanoids were mainly present in the flesh tissue.
THE IMPACT OF T CELL DEPLETION ON IMMUNE RECOVERY IN LUNG TRANSPLANT RECIPIENTS (2004)

O477 Aims: A strategy consisting of profound T cell depletion prior to transplantation (high dose anti-Thymoglobulin) followed by minimal immunosuppression (low dose tacrolimus and steroid) was initiated in lung transplant recipients. In this study we evaluate the humoral and cellular immune responses of thirty seven consecutive lung transplant recipients enrolled in this protocol to determine the impact on donor-specific alloreactivity and memory responses to pathogens. Methods: The immune monitoring consisted of sequential assessment of T cell subsets, B cells and DC subsets. Immune competence was determined by evaluating the PBMC in response to mitogens (ConA and PHA). Donor specific allo-sensitization was evaluated by the detection of allo-antibodies and by the proliferation and cell mediated cytotoxic responses to donor cells. Bronchoalveolar lavage cells (BAL) were also available for quantitative assessment of pro-inflammatory mediator gene expression (Granzyme β, IFN-γ, IL-15, MCP1, RANTES, TNF-α) using Taqman assays. Results: Immediately post-Tx we observed a sharp decline of T cell subsets and B cells. The recovery of CD8+ T cells occurred earlier than CD4+ cells (1 month vs. 4 months) while B cells recovered within 2 months. The frequency of DC1 at one year post-transplant (lin-,DR+, CD45+, CD11c+) was similar to normal controls while the DC2 subset (lin-,DR+,CD45+, CD123+) was significantly reduced. Con A and PHA responses recovered at 3 and 6 months post-Tx respectively. Anti-HLA specific antibodies were detected in 19/37 patients (12 pre-Tx, 7 de novo). Presence of donor-specific HLA antibodies early post-Tx (<4 months) in 5 patients was associated with severe ACR and augmented immunosuppression. During early ACR we observed elevated mRNA expression for macrophage activation markers (MCP1, RANTES and TNF- α) in BAL cells. However, late ACR (>5months) was associated with both elevation of mRNA of T helper 1 type mediators (Granzyme β and IFN- γ) and with macrophage activation. Conclusions: The comprehensive immune monitoring for humoral and cellular immunity of lung transplant recipients may promote better understanding of this new therapeutic approach and may also define the risk factors associated with allograft failure.
Virus Crystals as Nanocomposite Scaffolds (2005)

The generation of long-range three-dimensional nanoscopic patterns is a major goal in materials chemistry. Here we report a strategy for creating such systems using virus crystals as scaffolds which can be infiltrated with metal specifically palladium and platinum. The inorganic component effectively packs within the porous macromolecular crystal architecture, providing a route for patterning these materials on the nanometer length scale. To verify the quality of the metal infiltration, SEM-EDX was used to determine the homogeneous distribution of metal across the crystal, and TEM was used to confirm that the metal was confined within the porous structure of the crystal.
<title>Eradication of bacterial species via photosensitization</title> (1999)

Photosensitization and inactivation efficacy of three bacterial species: Prevotella nigrescens, Staphylococcus aureus and Escherichia coli have been investigated. Samples of Staphylococcus aureus and Escherichia coli were treated with the triphenylmethane dye malachite green isothiocyanate and exposed to light from a variety of continuous and pulsed light sauces at a wavelength of approximately 630 nm. Inactivation of the Gram-positive species Staphylococcus aureus was found to increase with radiation dose, whilst Gram-negative Escherichia coli was resistant to such treatment. Samples of the pigmented species Prevotella nigrescens were found to be inactivated by exposure to light alone. The mechanism of photosensitization and inactivation of Staphylococcus aureus with malachite green isothiocyanate is addressed. The possible roles of the excited triplet state of the photosensitizer, the involvement of molecular oxygen, and the bacterial cell wall are discussed. Photosensitization may provide a way of eliminating naturally pigmented species responsible for a variety of infections, including oral diseases such as gingivitis and periodontitis.
Proximity-based assays for the detection of activated HER3, HER2/HER3 heterodimers and HER3/PI3K complexes in formalin-fixed, paraffin-embedded cell line controls and tumors. (2009)

Abstract Abstract #4040 Although kinase-defective, the role of the HER3 receptor in driving tumor growth through dimerization with other HER family members is well recognized. There is increasing interest in developing therapeutic strategies to interfere with signaling through this receptor, either directly or indirectly. At the same time, there is recognition that the activation of HER3 could be an important biomarker of drug response and resistance. In particular the HER2/HER3 heterodimer has been extensively studied and, among all the possible homo and heterodimers formed by HER receptors, is considered the most mitogenic because of the ability of HER3 to effectively couple to the pro-survival PI3K/Akt pathway.&amp;#x2028; Using the VeraTag™ technology, we have developed a suite of assays designed to detect quantitatively the activation status of the HER3 receptor by measuring HER3-specific phosphorylation and formation of HER3 signaling complexes in formalin-fixed, paraffin-embedded (FFPE) cell line controls and tissue samples.These assays are dual antibody-based and measure complexes of proteins in close association since signal is generated only when the antibodies are bound to target-specific epitope sites proximal to one another. A capillary electrophoresis instrument equipped with laser-induced fluorescence provides a highly sensitive and quantitative read-out of the assay. We report data on assays which detect a ligand-induced, 2-5-fold change in HER2/HER3 heterodimer formation, a 10-20 fold change in phosphorylated HER3 signal and as high as a 10 fold change in HER3/PI3K complex formation in a series of cell line controls, spanning a wide range of HER2 and HER3 receptor levels. FFPE data were verified with results from co-immunoprecipitation using antibodies identical to those used in the VeraTag assay. The influence of the HER2 and HER3 levels on the formation of HER2/HER3 heterodimers and correlation with HER3 phosphorylation and formation of the PI3K adaptor complex will be discussed.&amp;#x2028; In addition, we have used these assays to landscape HER3 activation in a number of tissues, including breast and ovarian tumors, focusing particularly on HER2 positive breast cancer, where the HER2/HER3 heterodimer is thought to play a particularly significant role. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4040.