gebhart/patrepeval huggingface dataset:
Spermine induces haemoglobin synthesis in murine erythroleukaemia cells (1995)

The naturally occurring polyamine spermine induces haemoglobin synthesis in murine erythroleukaemia (MEL) cells. Haemoglobin production was accompanied by accumulation of cytoplasmic beta-globin mRNA and growth inhibition, but not by cell-cycle block or changes in cell volume. Hexamethylene-bisacetamide (HMBA), a well known differentiating agent, also induces haemoglobin production, but causes a G1 block and decreases cell volume. These findings indicate that HMBA and spermine affect MEL cells differently, even though both induce haemoglobin production.
Inhibition of Protein−Protein Association by Small Molecules:  Approaches and Progress (2002)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTInhibition of Protein−Protein Association by Small Molecules: Approaches and Progress†Peter L. ToogoodView Author Information Department of Medicinal Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105 Cite this: J. Med. Chem. 2002, 45, 8, 1543–1558Publication Date (Web):March 15, 2002Publication History Received10 October 2001Published online15 March 2002Published inissue 1 April 2002https://pubs.acs.org/doi/10.1021/jm010468shttps://doi.org/10.1021/jm010468sreview-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views3065Altmetric-Citations228LEARN 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:Inhibitors,Ligands,Peptides and proteins,Receptors,Small molecules Get e-Alerts
Cellular Reactions to Bone-Derived Material (1996)

Demineralized bone has been used as an acceptable alternative to fresh autogenous bone grafting in a variety of clinical reconstructive procedures. With the recent expansion of regional and national tissue banks, more implants are being used in routine applications. Questions raised about the bioactivity of human demineralized bone may be resolved by development of relevant assays for screening a lot of banked tissue. Such a bioassay could be developed based on the effects of osteoinductive materials on cells in vitro. Various effects of culture with demineralized bone or its components have been reported for cell lines or embryonic, fetal, or neonatal rodent and chick tissues and cells. In this study, human dermal fibroblasts and a variety of other cell types expressed features of chondroblastic phenotype when cultured with demineralized bone powder.
Electrical Contacts to Molecular Layers by Nanotransfer Printing (2003)

We introduce a novel approach, nanotransfer printing (nTP), to fabricate top-contact electrodes in Au/1,8-octanedithiol/GaAs junctions. Current−voltage and photoresponse experiments were conducted to evaluate the nature of electrical contact. Results show that the nTP method produces superior devices in which the electrical transport in nTP devices occurs through the 1,8-octanedithiol molecules. By contrast, conventional evaporation of Au onto the molecules results in direct Au/GaAs contacts. Thus, nTP is potentially useful for making electrical contacts in molecular electronics.
Dispersion-free fibre Bragg gratings (2002)

Fibre Bragg gratings with reduced/eliminated in-band dispersion are presented. When tested in add-drop configurations at 10 Gbit/s both 25 GHz and 50 GHz bandwidth gratings are shown to exhibit superior performance with no dispersion-induced penalties in the stopband. Furthermore, the demonstrated linear-phase Bragg gratings have >70% channel filling factor values and reflectivities in excess of 99.9%.
The molecular biology of recombination in Mycobacteria: what do we know and how can we use it? (2004)

Recombination is a ubiquitous genetic process which results in the exchange of DNA between two substrates. Homologous recombination occurs between DNA species with identical sequence whereas illegitimate recombination can occur between DNA with very little or no homology. Site-specific recombination is often used by temperate phages to stably integrate into bacterial chromosomes. Characterisation of the mechanisms of recombination in mycobacteria has mainly focussed on RecA-dependent homologous recombination and phage-directed site-specific recombination. In contrast the high frequency of illegitimate recombination in slow-growing mycobacteria has not been explained. The role of DNA repair in dormancy and infection have not yet been fully established, but early work suggests that RecA-mediated pathways are not required for virulence. All three recombination mechanisms have been utilised in developing genetic techniques for the analysis of the biology and pathogenesis of mycobacteria. A recently developed method for studying essential genes will generate further insights into the biology of these important organisms.
Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism (1994)

Inflammation is characterized by migration of neutrophils through the endothelium, and the chemokine interleukin-8 (IL-8) appears to be involved. We asked whether adherence of cells bearing a membrane-form of interleukin 1 (IL-1) induces IL-8 secretion from human umbilical vein endothelial cells (HUVEC) and fibroblasts. Human peripheral blood mononuclear cells (PBMC) were stimulated with endotoxin for 12 hours and then fixed for 4 hours with paraformaldehyde. When these cells were added to HUVEC or fibroblasts, IL-8 production was induced. This stimulation by fixed PBMC was attributed to IL-1, because pretreatment of HUVEC or fibroblasts with IL-1 receptor antagonist (IL-1Ra) reduced the induction by 95% and 80%, respectively, P < .005. Using anti-IL-1 alpha monoclonal antibodies, reduction was complete, whereas anti-IL-1 beta had no effect. IL-1 alpha was shown on the surface of monocytes by fluorescence-activated cell sorter (FACS) analysis. Blockade of IL-1 receptors on PBMC did not affect the activity of membrane-associated IL-1 alpha, indicating that IL-1 is not anchored to the membrane through its receptors. However, PBMC treated with D-mannose before fixation resulted in a loss of activity; this loss of activity was associated with release of IL-1 alpha, not IL-1 beta, into the supernatant. Thus, anchoring of IL-1 alpha to the membrane may be via a lectin or mannose receptor-like interaction. Blockade of membrane IL-1 alpha required a 30-fold and fivefold excess of IL-1Ra compared with the amount required to block soluble IL-1 beta and IL-1 alpha, respectively. We conclude that the fixed PBMC IL-8 inducing activity is almost entirely caused by IL-1, that this represents IL-1 alpha bound to a surface lectin or mannose receptor on the monocyte, and that it functions in inflammation via juxtacrine interactions.
Persistence of HIV‐1 silent infection in seronegative subjects at high risk (1991)

Abstract Twenty regular sexual partners of HIV‐1 infected subjects, without detectable human irnmunodeficiency virus (HIV‐1) antibody and positive for HIV‐1 genome by in situ hybridization (ISH), were selected and studied longitudinally for 6–36 months to estimate the duration of silent infection. During the follow‐up period, 10 showed atypical Western Blot (WB) patterns. Two seronegative partners seroconverted. Rapid progress t o AIDS was observed in 7 seropositive subjects.
Resuscitating Mutations in a Furin Cleavage-Deficient Mutant of the Flavivirus Tick-Borne Encephalitis Virus (2005)

Cleavage of the viral surface protein prM by the proprotein convertase furin is a key step in the maturation process of flavivirus particles. A mutant of tick-borne encephalitis virus (TBEV) carrying a deletion mutation within the furin recognition motif of protein prM (changing R-T-R-R to R-T-R) was previously shown to be noninfectious in BHK-21 cells. We now demonstrate how natural selection can overcome this lethal defect in two different growth systems by distinct resuscitating mutations. In BHK-21 cells, a spontaneous codon duplication created a minimal furin cleavage motif (R-R-T-R). This mutation restored infectivity by enabling intracellular prM cleavage. A completely different mutation pattern was observed when the mutant virus was passaged in mouse brains. The "pr" part of protein prM, which is removed by cleavage, contains six conserved Cys residues. The mutations selected in mice changed the number of Cys residues to five or seven by substitution mutations near the original cleavage site, probably causing a major perturbation of the structural integrity of protein prM. Although viable in mice, such Cys mutants could not be passaged in BHK-21 cells under normal growth conditions (37 degrees C), but one of the mutants exhibited a low level of infectivity at a reduced incubation temperature (28 degrees C). No evidence for the cleavage of protein prM in BHK-21 cells was obtained. This suggests that under certain growth conditions, the structural perturbation of protein prM can restore the infectivity of TBEV by circumventing the need for intracellular furin-mediated cleavage. This is the first example of a flavivirus using such a molecular mechanism.
U6 snRNA genes ofArabidopsisare transcribed by RNA polymerase III but contain the same two upstream promoter elements as RNA polymerase ll-transcribed U-snRNA genes (1990)

Previously we have demonstrated that the U2 snRNA genes from the higher plant Arabidopsis thaliana contain two upstream elements, the USE with sequence RTCCCACATCG and a -30 'TATA' box, which are essential for transcription by RNA polymerase II, and that the conserved spacing of about four helical DNA turns between these elements is important for optimal promoter function. We have now isolated three genes encoding U6 RNA in Arabidopsis. Transcription of these genes in transfected protoplasts of Nicotiana plumbaginifolia is resistant to alpha-amanitin indicating that they are transcribed by RNA polymerase III. The upstream regions of three Arabidopsis U6 genes contain USE and -30 TATA-like elements similar to those found to be important for transcription of U2 RNA genes but the spacing between the two elements is about 10 bp closer than in the U2 genes. Using synthetic U6 genes we demonstrate that the USE and TATA elements are indispensable for their transcription, the TATA boxes of U2 and U6 genes are interchangeable, and that the intragenic A box-like sequence of U6 gene is not essential. Increasing the distance between the USE and TATA by 10 bp inactivates U6 gene transcription, demonstrating that proper positioning of the elements is also important for transcription by RNA polymerase III. The data indicate that the structure of U-snRNA gene promoters and the determinants of polymerase specificity are completely different between vertebrates and plants.
Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension (2016)

Pulmonary arterial hypertension (PAH) is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database. We identified 228 differentially expressed genes (DEGs) from a rat PAH model caused by inhibition of vascular endothelial growth factor receptor under hypoxic conditions, 379 DEGs from a mouse PAH model associated with systemic sclerosis, 850 DEGs from a mouse PAH model associated with schistosomiasis, 1598 DEGs from one cohort of human PAH patients, and 4260 DEGs from a second cohort of human PAH patients. Gene-by-gene comparison identified four genes that were differentially upregulated or downregulated in parallel in all five sets of DEGs. Expression of coiled-coil domain containing 80 (CCDC80) and anterior gradient two genes was significantly increased in the five datasets, whereas expression of SMAD family member six and granzyme A was significantly decreased. Weighted gene co-expression network analysis revealed a connection between CCDC80 and collagen type I alpha 1 (COL1A1) expression. To validate the function of CCDC80 in vivo, we knocked out ccdc80 in zebrafish using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. In vivo imaging of zebrafish expressing a fluorescent protein in endothelial cells showed that ccdc80 deletion significantly increased the diameter of the ventral artery, a vessel supplying blood to the gills. We also demonstrated that expression of col1a1 and endothelin-1 mRNA was significantly decreased in the ccdc80-knockout zebrafish. Finally, we examined Ccdc80 immunoreactivity in a rat PAHmodel and found increased expression in the hypertrophied media and adventitia of the pre-acinar pulmonary arteries (PAs) and in the thickened intima, media, and adventitia of the obstructed intra-acinar PAs. These results suggest that increased expression of CCDC80 may be involved in the pathogenesis of PAH, potentially by modulating the expression of endothelin-1 and COL1A1.
Visualization of Pit-1 Transcription Factor Interactions in the Living Cell Nucleus by Fluorescence Resonance Energy Transfer Microscopy (1998)

The pituitary-specific transcription factor Pit-1 forms dimers when interacting with specific DNA elements and has been shown to associate with several other nuclear proteins. Recently, techniques have become available that allow visualization of protein-protein interactions as they occur in single living cells. In this study, the technique of fluorescence resonance energy transfer (FRET) microscopy was used to visualize the physical interactions of Pit-1 proteins fused to spectral variants of the jellyfish green fluorescent protein (GFP) that emit green or blue light [blue fluorescent protein (BFP)]. An optimized imaging system was used to discriminate fluorescence signals from single cells coexpressing the BFP- and GFP-fusion proteins, and the contribution of spectral overlap to background fluorescence detected in the FRET images was established. Energy transfer signals from living cells expressing a fusion protein in which GFP was tethered to BFP by short protein linker was used to demonstrate acquisition of FRET signals. Genetic vectors encoding GFP- and BFP-Pit-1 proteins were prepared, and biological function of the fusion proteins was confirmed. FRET microscopy of HeLa cells coexpressing the GFP- and BFP-Pit-1 demonstrated energy transfer, which required the two fluorophores to be separated by less than 100 A. Biochemical studies previously demonstrated that Pit-1 physically interacts with both c-Ets-1 and the estrogen receptor. FRET imaging of cells coexpressing BFP-Pit-1 and GFP-Ets-1 demonstrated energy transfer between these fusion proteins, a result consistent with their association in the nucleus of these living cells. In contrast, there was no evidence for energy transfer between the BFP-Pit-1 and an estrogen receptor-GFP fusion proteins. It is likely that the FRET imaging approach described here can be applied to many different protein-partner pairs in a variety of cellular contexts.
Find this for me (2011)

With all the information available on the web, there is a growing need to provide mobile access to this information for the large, growing population of mobile internet users. In this paper, we propose a solution to the problem of open web mobile information retrieval, by conducting a dialogue with the user over a simple text-based interface. Using techniques from NLP, web page analysis, and information extraction, our approach automatically navigates web sites on the user's behalf and extracts specific information from those sites to present to the user textually. Empirical evaluation shows that our approach to open web information retrieval is feasible, and a qualitative evaluation validates that such a system meets user needs for mobile information access.
Simultaneous Signal and Noise Modeling via the Radon Transform (2004)

D029 SIMULTANEOUS SIGNAL AND NOISE MODELING VIA THE RADON TRANSFORM M.D. SACCHI 1 C. MOLDOVEANU-CONSTANTINESCU 1 and D. TRAD 2 1 University of Alberta Department of Physics Institute for Geophysical Research Edmonton AB Canada T6G 1W2 2 Veritas Geo-services Calgary Summary The decomposition and filtering of coherent noise is a long standing problem in exploration seismology. Low velocity events (air wave surface waves or ground roll) tend to produce large energy signals that complicate the identification and enhancement of seismic reflections. This problem can be alleviated by filtering the offending low velocity signals using for instance ¡ £ filters.
Protease-induced immunoregulatory activity of platelet factor 4. (1986)

Intravenous injection of human or mouse serum or platelet material secreted from appropriately stimulated platelets ("releasate") together with antigen alleviates the immunosuppression in SJL/J mice induced by injection of irradiated lymphoma cells or in (CB6)F1 mice induced by injection of concanavalin A. We now report that injection of releasate from 10(6) human platelets restores plaque-forming cells to the unsuppressed number; greater amounts increase responses further. Immunoregulatory activity is released from platelets exposed to thrombin in parallel with other alpha-granule components. Heparin-agarose absorbs activity. Purified platelet factor 4 (PF4) has activity; beta-thromboglobulin and platelet-derived growth factor have little or none. Activity in serum is neutralized by goat anti-human PF4. An enzymatic step is necessary for production of immunoregulatory activity. Releasates boiled immediately after platelet aggregation with 250 nM A23187 or those produced by adding A23187 in the presence of 100 microM serine protease inhibitor (p-amidinophenyl)methanesulfonyl fluoride (APMSF) are ineffective, whereas releasates boiled or mixed with APMSF after incubation for 60 min are active. Activity is generated by incubating a mixture of heparin-absorbed releasate (as enzyme source) and heparin-agarose eluate of releasate made in the presence of APMSF (as substrate source). The enzymatic step does not alter the heparin-neutralizing activity of PF4. Apparently a secreted platelet protease converts PF4 to a form with immunoregulatory activity.
RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types (2019)

The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 immune cell types within the peripheral blood mononuclear cell (PBMC) fraction of healthy donors using RNA-seq (RNA sequencing) and flow cytometry. Our dataset was used, first, to identify sets of genes that are specific, are co-expressed, and have housekeeping roles across the 29 cell types. Then, we examined differences in mRNA heterogeneity and mRNA abundance revealing cell type specificity. Last, we performed absolute deconvolution on a suitable set of immune cell types using transcriptomics signatures normalized by mRNA abundance. Absolute deconvolution is ready to use for PBMC transcriptomic data using our Shiny app (https://github.com/giannimonaco/ABIS). We benchmarked different deconvolution and normalization methods and validated the resources in independent cohorts. Our work has research, clinical, and diagnostic value by making it possible to effectively associate observations in bulk transcriptomics data to specific immune subsets.
High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. (1992)

Analysis of untreated fresh blood plasma from healthy, fasting donors revealed that high density lipoprotein (HDL) particles carry most (approximately 85%) of the detectable oxidized core lipoprotein lipids. Low density lipoprotein (LDL) lipids are relatively peroxide-free. In vitro the mild oxidation of gel-filtered plasma from fasting donors with a low, steady flux of aqueous peroxyl radicals initially caused preferential oxidation of HDL rather than LDL lipids until most ubiquinol-10 present in LDL was consumed. Thereafter, LDL core lipids were oxidized more rapidly. Isolated lipoproteins behaved similarly. Preferential accumulation of lipid hydroperoxides in HDL reflects the lack of antioxidants in most HDL particles compared to LDL, which contained 8-12 alpha-tocopherol and 0.5-1.0 ubiquinol-10 molecules per particle. Cholesteryl ester hydroperoxides (CEOOHs) in HDL and LDL were stable when added to fresh plasma at 37 degrees C for up to 20 hr. Transfer of CEOOHs from HDL to LDL was too slow to have influenced the in vitro plasma oxidation data. Incubation of mildly oxidized LDL and HDL with cultured hepatocytes afforded a linear removal of CEOOHs from LDL (40% loss over 1 hr), whereas a fast-then-slow biphasic removal was observed for HDL. Our data show that HDL is the principal vehicle for circulating plasma lipid hydroperoxides and suggest that HDL lipids may be more rapidly oxidized than those in LDL in vivo. The rapid hepatic clearance of CEOOHs in HDL could imply a possible beneficial role of HDL by attenuating the build-up of oxidized lipids in LDL.
Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology (1998)

The pineal hormone melatonin is secreted with a marked circadian rhythm. Normally, maximum production occurs during the dark phase of the day and the duration of secretion reflects the duration of the night. The changing profile of secretion as a function of daylength conveys photoperiodic information for the organization of seasonal rhythms in mammals. The role of melatonin in mammalian circadian physiology is less clear. However, exogenous melatonin can phase shift, and in some cases entrain, circadian rhythms in rodents and humans. It can also lower body temperature and induce transient sleepiness. These properties indicate that melatonin can be used therapeutically in circadian rhythm disorder. Successful outcomes have been reported, for example in jet lag and shift work, and with cyclic sleep disorder of some blind subjects. Melatonin receptors of several subtypes are found in the brain, the retina, the pituitary and elsewhere. They are currently under intense investigation. Melatonin agonists and antagonists are under development.
A New Method for the Dressing of Free Skin Grafts (1990)

Using adhesive drapes and a disposable suction drain, a new method for the dressing of free skin grafts has been devised. The graft is compressed by pressure that is equivalent to the negative pressure of the suction drain. This method can apply uniform and constant pressure on the graft. Moreover, the graft can be observed through a transparent drape so that the existence of hematomas can be detected easily.