gebhart/patrepeval huggingface dataset:
Estimation and comparison of lysosomal and cytoplasmic pH of human fibroblasts from healthy donors and patients with lysosomal storage diseases. (1991)

Measurements were made of the pH of cytoplasm and lysosomes of cultured skin fibroblasts from healthy donors and from patients with lysosomal storage diseases (mannosidosis, Fabry's disease, and Krabbe's disease), and the effects of sucrose loading on normal fibroblasts were studied. The cytoplasmic pH of the pathological cells did not differ from control values, but the intralysosomal pH was significantly higher in sucrose-loaded normal fibroblasts and in cells from a patient with mannosidosis and from another with Fabry's disease. The change in pH observed accorded with an increase in size of the organelles, owing to accumulation of nonhydrolyzable compounds. In fibroblasts from a patient with Krabbe's disease, which do not store nonhydrolyzable compounds, there was no increase either in intralysosomal pH or in lysosome size. It is suggested that the decrease in the pH difference between the cytoplasm and lysosomes in the pathological cells leads to inhibition of catabolic processes in lysosomes and to some changes in the intracellular transport of these vesicles.
Mechanisms of Immune Injury in Multiple Sclerosis (1996)

In this review, we address current concepts regarding the mechanisms of tissue damage that lead to demyelination and oligodendrocyte loss in multiple sclerosis. Particular emphasis has been placed on examining the MS lesion for evidence for pathogenetic processes that have been implicated from various in vivo and in vitro model systems. Central in this analysis has been the evaluation of the various effector cell types and their products. The results strongly support the conclusion that proinflammatory cytokines are major mediators of tissue damage, through the activation of inflammatory cells and resident glial cells. A role for antibody is also discussed, particularly as part of an antibody-dependent cell mediated demyelinating process. Minor populations of lymphocytes may also participate by defining the nature of the immunological microenvironment.
Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis (2010)

Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients develop autoantibodies to DNA, histones, and often to neutrophil proteins. These form immune complexes that are pathogenic and may cause lupus nephritis. In SLE patients, infections can initiate flares and are a major cause of mortality. Neutrophils respond to infections and release extracellular traps (NETs), which are antimicrobial and are made of DNA, histones, and neutrophil proteins. The timely removal of NETs may be crucial for tissue homeostasis to avoid presentation of self-antigens. We tested the hypothesis that SLE patients cannot clear NETs, contributing to the pathogenesis of lupus nephritis. Here we show that serum endonuclease DNase1 is essential for disassembly of NETs. Interestingly, a subset of SLE patients' sera degraded NETs poorly. Two mechanisms caused this impaired NET degradation: (i) the presence of DNase1 inhibitors or (ii) anti-NET antibodies prevented DNase1 access to NETs. Impairment of DNase1 function and failure to dismantle NETs correlated with kidney involvement. Hence, identification of SLE patients who cannot dismantle NETs might be a useful indicator of renal involvement. Moreover, NETs might represent a therapeutic target in SLE.
Microenvironment-Derived HGF Overcomes Genetically Determined Sensitivity to Anti-MET Drugs (2014)

Cell-based drug screenings indicate that tumors displaying c-MET gene amplification are "addicted" to MET signaling and therefore are very sensitive to MET-targeted agents. However, these screenings were conducted in the absence of the MET ligand, hepatocyte growth factor (HGF), which is abundant in the tumor microenvironment. Sensitivity of six MET-addicted human tumor cells to three MET kinase inhibitors (JNJ-38877605, PHA-665752, crizotinib) and one antagonistic anti-MET antibody (DN30 Fab) was analyzed in the absence or presence of HGF, in a stroma-tumor coculture system, and by combining anti-MET drugs with an HGF neutralizing antibody (ficlatuzumab) in human HGF knock-in mice bearing c-MET-amplified tumors. In all models examined, HGF promoted resistance to MET-targeted agents, affecting both their potency and efficacy. HGF-induced resistance was due to restoration of physiologic GAB1-mediated PI3K activation that compensated for loss of aberrant HER3-dependent PI3K signaling. Ficlatuzumab restored sensitivity to MET-targeted agents in coculture systems and overcame resistance to JNJ-38877605, crizotinib, and DN30 Fab in human HGF knock-in mice. These data suggest that c-MET-amplified tumor cells-which normally exhibit ligand-independent, constitutive MET activation-become dependent on HGF for survival upon pharmacologic MET inhibition. Because HGF is frequently overexpressed in human cancer, this mechanism may represent a major cause of resistance to anti-MET therapies. The ability of ficlatuzumab to overcome HGF-mediated resistance generates proof of principle that vertical inhibition of both a tyrosine kinase receptor and its ligand can be therapeutically beneficial and opens new perspectives for the treatment of MET-dependent tumors.
Simplification of high-energy collision spectra of peptides by amino-terminal derivatization (1993)

Four-sector tandem mass spectrometry proves extremely useful for providing sequence information for peptides. The complexity of ion fragmentations, however, makes data interpretation difficult and time consuming. Attachment of a fixed positive charge to the peptide amino terminus forces production of only N-terminal fragment ions to yield simplified, predictable fragmentation. Reaction of a peptide at pH 6 with iodoacetic anhydride selectively modifies the N-terminus by exploiting the pK(a) differences between the alpha-amino group and any lysine side-chain epsilon-amino groups. The iodoacetyl peptide can react with many reagents to form a fixed positive charge. We find reaction with dimethyloctylamine forms a quaternary ammonium derivative with good surface activity properties and concomitant increased sensitivity. The high-energy CAD fragment ion spectra of the N-terminally derivatized peptides show predominantly a(n) and d(n) ions. The abundant d(n) ions permit ready distinction of leucine and isoleucine. Fewer fragment ions make data interpretation simpler and lead to more intense peaks since the ion intensity is spread among fewer peaks. The method is particularly useful for peptides which do not otherwise yield sufficient fragmentation to provide either the complete sequence or the locations of modified amino acids.
Revisiting Monomeric HIV-1 Protease (2003)

Interactions between the C-terminal interface residues (96-99) of the mature HIV-1 protease were shown to be essential for dimerization, whereas the N-terminal residues () and Arg(87) contribute to dimer stability (Ishima, R., Ghirlando, R., Tozser, J., Gronenborn, A. M., Torchia, D. A., and Louis, J. M. (2001) J. Biol. Chem. 276, 49110-49116). Here we show that the intramonomer interaction between the side chains of Asp(29) and Arg(87) influences dimerization significantly more than the intermonomer interaction between Asp(29) and Arg(8'). Several mutants, including T26A, destablize the dimer, exhibit a monomer fold, and are prone to aggregation. To alleviate this undesirable property, we designed proteins in which the N- and C-terminal regions can be linked intramolecularly by disulfide bonds. In particular, cysteine residues were introduced at positions 2 and 97 or 98. A procedure for the efficient preparation of intrachain-linked polypeptides is presented, and it is demonstrated that the Q2C/L97C variant exhibits a native-like single subunit fold. It is anticipated that monomeric proteases of this kind will aid in the discovery of novel inhibitors aimed at binding to the monomer at the dimerization interface. This extends the target area of current inhibitors, all of which bind across the active site formed by both subunits in the active dimer.
Control of Gel Morphology and Properties of a Class of Metallo-Supramolecular Polymers by Good/Poor Solvent Environments (2008)

Through the utilization of a mixed solvent system, consisting of a good solvent (DMSO) with either a nonsolvent (water) or a poor solvent (ethylene glycol), the morphology and properties of a class of stimuli-responsive metallo-supramolecular gels can be systematically tailored. These gels are formed via self-assembly of a ditopic ligand, consisting of a 2,6-bis(1′-methylbenzimidazolyl)-4-oxypyridine moiety attached to either end of a penta(ethylene glycol) core, in the presence of a transition metal ion (ZnII). In each solvent system, a composition window is located in which gels, varying in turbidity from highly opaque (water- or ethylene glycol-rich) to highly transparent (DMSO-rich), are formed. Morphological observations suggest gelation occurs by a common mechanism throughout the composition range, i.e., via the flocculation of semicrystalline colloidal particles. Increase of DMSO content leads to a reduction in the particle size, accompanied by an increase in sol concentration. WAXD and SAXS analysis indicates that the degree of crystallinity of the colloidal particles is dramatically decreased compared with those formed in a previous study using acetonitrile as solvent but that a new lamellar organization develops as the DMSO content increases, evidently reflecting incorporation of the good solvent into the network structure. These structural changes are accompanied by an increase in the shear storage modulus of the gel up to a maximum value, beyond which the modulus decreases. Thus, by tailoring the solvent composition, it is possible to produce highly transparent gels that, while very strong, are highly mechano-responsive; i.e., they exhibit pronounced yielding and thixotropic behavior.
Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor α: Findings in open-label and randomized placebo-controlled trials (2000)

Anti-dsDNA antibodies of IgM class are induced by infliximab therapy; the frequency is dependent on the assay method used. Only 1 of the 156 patients who were treated with infliximab developed a self-limiting clinical lupus syndrome; that patient developed high titers of anti-dsDNA antibodies of IgG, IgM, and IgA class, as detected by the CLIFT and by 2 different Farr assays.
Antibiotic susceptibility of potentially probiotic Bifidobacterium isolates from the human gastrointestinal tract (1998)

Sixteen Bifidobacterium isolates from the human gastrointestinal tract were assayed for susceptibility to 44 antibiotics by soft agar overlay disc diffusion on TPY agar. Five isolates (3/7 B. bifidum and 2/3 B. breve) exhibited atypical antibiotic susceptibility profiles. Poor growth in the agar overlay accounted for susceptibility of B. bifidum but not B. breve isolates. All other isolates were resistant to cefoxitin (30 micrograms), aztreonam (30 micrograms), vancomycin (30 micrograms), amikacin (30 micrograms), gentamicin (10 micrograms), kanamycin (30 micrograms), streptomycin (10 micrograms), fusidic acid (10 micrograms), trimethoprim (5 micrograms), norfloxacin (10 micrograms), nalidixic acid (30 micrograms), metronidazole (5 micrograms), polymyxin B (300 micrograms) and colistin sulphate (10 micrograms), and they were susceptible to the six penicillins studied, cephalothin (30 micrograms), cefuroxime (30 micrograms), cefaclor (30 micrograms), ceftizoxime (30 micrograms), cefotaxime (30 micrograms), bacitracin (10 micrograms), chloramphenicol (30 micrograms), erythromycin (15 micrograms), clindamycin (2 micrograms), rifampicin (5 micrograms) and nitrofurantoin (300 micrograms). In addition, they varied in their susceptibility to cephradine (30 micrograms), cephazolin (30 micrograms), cefoperazone (75 micrograms), ceftriaxone (30 micrograms), ofloxacin (5 micrograms) and furazolidone (15 micrograms). They were resistant, or only marginally moderately susceptible, to ceftazidime (30 micrograms), netilmicin (10 micrograms), sulphamethoxazole (100 micrograms), cotrimoxazole (25 micrograms) and ciprofloxacin (5 micrograms), and susceptible or marginally moderately susceptible to tetracycline (30 micrograms). All B. bifidum isolates were susceptible to cefixime (5 micrograms). Four microorganism-drug combinations were evaluated for beta-lactamase activity but its absence suggested that cell wall impermeability was responsible for cephalosporin resistance among bifidobacteria. The antibiotic susceptibility of B. animalis 25527T was similar to that of the human isolates.
Identification of a Light-Responsive Region of the Nuclear Gene Encoding the B Subunit of Chloroplast Glyceraldehyde 3-Phosphate Dehydrogenase from Arabidopsis thaliana (1994)

We report here the identification of a cis-acting region involved in light regulation of the nuclear gene (GapB) encoding the B subunit of chloroplast glyceraldehyde 3-phosphate dehydrogenase from Arabidopsis thaliana. Our results show that a 664-bp GapB promoter fragment is sufficient to confer light induction and organ-specific expression of the Escherichia coli beta-glucuronidase reporter gene (Gus) in transgenic tobacco (Nicotiana tabacum) plants. Deletion analysis indicates that the -261 to -173 upstream region of the GapB gene is essential for light induction. This region contains four direct repeats with the consensus sequence 5'-ATGAA(A/G)A-3' (Gap boxes). Deletion of all four repeats abolishes light induction completely. In addition, we have linked a 109-bp (-263 to -152) GapB upstream fragment containing the four direct repeats in two orientations to the -92 to +6 upstream sequence of the cauliflower mosaic virus 35S basal promoter. The resulting chimeric promoters are able to confer light induction and to enhance leaf-specific expression of the Gus reporter gene in transgenic tobacco plants. Based on these results we conclude that Gap boxes are essential for light regulation and organ-specific expression of the GapB gene in A. thaliana. Using gel mobility shift assays we have also identified a nuclear factor from tobacco that interacts with GapA and GapB DNA fragments containing these Gap boxes. Competition assays indicate that Gap boxes are the binding sites for this factor. Although this binding activity is present in nuclear extracts from leaves and roots of light-grown or dark-treated tobacco plants, the activity is less abundant in nuclear extracts prepared from leaves of dark-treated plants or from roots of greenhouse-grown plants. In addition, our data show that this binding factor is distinct from the GT-1 factor, which binds to Box II and Box III within the light-responsive element of the RbcS-3A gene of pea.
Expansion microscopy of zebrafish for neuroscience and developmental biology studies (2017)

Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses. Finally, ExM could resolve subsynaptic protein organization, such as ring-like structures composed of glycine receptors. Regarding development, we used ExM to characterize the shapes of nuclear invaginations and channels, and to visualize cytoskeletal proteins nearby. We detected nuclear invagination channels at late prophase and telophase, potentially suggesting roles for such channels in cell division. Thus, ExM of the larval and embryonic zebrafish may enable systematic studies of how molecular components are configured in multiple contexts of interest to neuroscience and developmental biology.
Impurities in silicon solar cells (1980)

The effects of various metallic impurities, both singly and in combinations, on the performance of silicon solar cells have been studied. Czochralski crystals were grown with controlled additions of secondary impurities. The primary dopants were boron and phosphorus while the secondaires were: A1, B, C, Ca, Co, Cr, Cu, Fe, Mg, Mn, Mo, Nb, P, Pd, Ta, Ti, V, W, Zn, and Zr. Impurity concentrations ranged from 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">10</sup> to 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">17</sup> /cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> . Solar cells were made using a conventional diffusion process and were characterized by computer reduction of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I-V</tex> data. The collected data indicated that impurity-induced performance loss was primarily due to reduction of the base diffusion length. Based on this observation, an analytic model was developed which predicts cell performance as a function of the secondary impurity concentrations. The calculated performance parameters are in good agreement with measured values except for Cu, Ni, and Fe, which at higher concentrations, degrade the cell substantially by means of junction mechanisms. This behavior can be distinguished from base diffusion length effects by careful analysis of the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I-V</tex> data. The effects of impurities in n-base and p-base devices differ in degree but submit to the same modeling analysis. A comparison of calculated and measured performance for multiple impurities indicates a limited interaction between impurities, e.g., copper appears to improve titanium-doped cells.
Modelling distribution and abundance with presence‐only data (2005)

Summary Presence‐only data, for which there is no information on locations where the species is absent, are common in both animal and plant studies. In many situations, these may be the only data available on a species. We need effective ways to use these data to explore species distribution or species use of habitat. Many analytical approaches have been used to model presence‐only data, some inappropriately. We provide a synthesis and critique of statistical methods currently in use to both estimate and evaluate these models, and discuss the critical importance of study design in models where only presence can be identified Profile or envelope methods exist to characterize environmental covariates that describe the locations where organisms are found. Predictions from profile approaches are generally coarse, but may be useful when species records, environmental predictors and biological understanding are scarce. Alternatively, one can build models to contrast environmental attributes associated with known locations with a sample of random landscape locations, termed either ‘pseudo‐absences’ or ‘available’. Great care needs to be taken when selecting random landscape locations, because the way in which they are selected determines the modelling techniques that can be applied. Regression‐based models can provide predictions of the relative likelihood of occurrence, and in some situations predictions of the probability of occurrence. The logistic model is frequently applied, but can rarely be used directly to estimate these models; instead, case–control or logistic discrimination should be used depending on the sample design. Cross‐validation can be used to evaluate model performance and to assess how effectively the model reflects a quantity proportional to the probability of occurrence. However, more research is needed to develop a single measure or statistic that summarizes model performance for presence‐only data. Synthesis and applications. A number of statistical procedures are available to explore patterns in presence‐only data; the choice among them depends on the quality of the presence‐only data. Presence‐only records can provide insight into the vulnerability, historical distribution and conservation status of species. Models developed using these data can inform management. Our caveat is that researchers must be mindful of study design and the biases inherent in presence data, and be cautious in the interpretation of model predictions.
Trends in biochemistry and enzymology of cellulose degradation (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrends in biochemistry and enzymology of cellulose degradationA. A. KlyosovCite this: Biochemistry 1990, 29, 47, 10577–10585Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://doi.org/10.1021/bi00499a001Request reuse permissionsArticle Views1219Altmetric-Citations144LEARN 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 InReddit PDF (1 MB) Get e-Alertsclose Get e-Alerts
Percutaneous aspiration of a coronary thrombus (1989)

Abstract Right coronary artery occlusion by a thrombus occurred during the coronary angiography performed in a patient with anterior myocardial infarction. Emergency coronary aspiration was undertaken via a 9F guiding catheter, which allowed the thrombus to be removed. The patient, who was in cardiogenic shock, immediately improved and was subsequently discharged without any complications or sequelae.
Tracking football players with multiple cameras (2006)

Sports scenarios present an interesting challenge for visual surveillance applications. Here, we describe a system, and a set of techniques, for tracking players in a football (soccer) environment. The system input is video data from static cameras with overlapping fields-of-view at a football stadium. The output is the real-world, real-time positions of football players during a match. In this chapter, we discuss the problems and solutions that have arisen whilst designing systems and algorithms for this purpose.