gebhart/patrepeval huggingface dataset:
Cellular and Molecular Regulation of Hematopoietic and Intestinal Stem Cell Behavior (2005)

Two fundamental questions in stem cell research are what controls stem cell number in vivo and which signal pathways regulate self-renewal. Here we summarize our recent studies regarding the role of BMP signaling in regulation of stem cell behavior in both the hematopoietic and intestinal systems. These studies provide evidence to show that BMP signaling plays an important role in controlling stem cell number, at least in these two stem cell compartments. However, the BMP signal utilizes different mechanisms to fulfill this purpose: in the hematopoietic stem cell compartment it controls stem cell number through regulation of the niche size; in the intestinal stem cell compartment it directly controls self-renewal of stem cells through restriction of Wnt/beta-catenin activity. The Bmpr1a mutant mouse provided an elegant model which allowed us to identify the HSC niche, an enigma for more than 25 years. Our work provided more evidence to demonstrate the essential function of the niche in maintenance of stem cells and showed that multiple signals are required to maintain a balanced control of stem cell self-renewal.
El impacto de la ampliación sobre la proyección exterior de la UE (2004)

La proxima ronda de ampliacion de la UE, la mayor y mas compleja de toda su historia tendra repercusiones ?algunas de ellas muy importantes? sobre la proyeccion y la actividad internacionales de la Union Europea. Este articulo pretende acercarse a los impactos posibles de la ampliacion sobre las relaciones exteriores de la UE, evaluando tres de los ambitos en los que estos impactos pueden ser mayores: la politica de cooperacion, las relaciones comerciales y las relaciones politicas. De este analisis se deriva un diseno del marco general en que se manifestaran las consecuencias de la ampliacion, que sera diferenciado, atendiendo al interes estrategico de la UE, tanto en areas geograficas o paises, como en politicas particulares.
Engineered tRNA suppression of a CFTR nonsense mutation (2016)

Abstract Ten percent of human diseases are caused by ‘nonsense’ mutations that lead to premature truncation of the protein reading frame. Small molecules that promote read-through of such PTC have significant clinical promise but current iterations suffer from low in vivo efficacy and the nonselective amino acid incorporation. Alternatively, while gene-modifying approaches, such as CRISPR/Cas9, represent a long-term solution, such treatments may be far from reaching the clinical setting. Building on previous work by our group and others, we describe a tRNA engineering approach that enables the conversion of an in frame nonsense stop mutation to the naturally occurring amino acid, thus rescuing the full-length wild type protein. Data is presented demonstrating the functionality of the approach with the rescue of CFTR W1282X, a human mutation that causes cystic fibrosis (CF). The stringency of the approach is confirmed by mass spectrometry in a model protein indicating the encoding of only tryptophan at the TGA suppression site. The data describe the first use of an edited tRNA to repair a CF causative mutation and serve a proof of principle for the eventual use of codon-edited tRNA for the therapeutic rescue of PTC disease codons.
Treatment of murine lupus with monoclonal anti-T cell antibody. (1985)

Three strains of autoimmune mice (MRL/lpr, NZB/NZW, and BXSB) were treated with repeated injections of rat monoclonal anti-T cell antibody (anti-Thy-1.2) in order to determine 1) the extent and duration of target cell depletion, 2) the effect of T cell depletion on the course of autoimmunity, and 3) the magnitude and consequences of the host immune response to the monoclonal antibody. Mice were treated with 6 mg of anti-Thy-1.2 every 2 wk beginning early in their disease. Treatment produced a substantial reduction in circulating T cells in all three strains. Therapy was beneficial in MRL/lpr mice. It reduced lymphadenopathy, lowered autoantibody concentrations, retarded renal disease, and prolonged life. In contrast, treatment did not improve autoimmunity in NZB/NZW mice, and it caused fatal anaphylaxis in BXSB mice. These findings demonstrate that monoclonal antilymphocyte antibodies can serve as specific probes to examine the cells that contribute to autoimmunity. Moreover, they illustrate the potential therapeutic value of monoclonal antilymphocyte antibodies when a pathogeneic cell subset can be identified. However, the same antibody may have a broad range of effects, from efficacy to severe toxicity, even in diseases that share clinical features.
Angiogenesis and chemokines in rheumatoid arthritis and other systemic inflammatory rheumatic diseases (2002)

Angiogenesis, the formation of new vessels, is important in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. Chemotactic cytokines termed chemokines mediate the ingress of leukocytes, including neutrophils and monocytes into the inflamed synovium. In this review, authors discuss the role of the most important angiogenic factors and angiogenesis inhibitors, as well as relevant chemokines and chemokine receptors involved in chronic inflammatory rheumatic diseases. RA was chosen as a prototype to discuss these issues, as the majority of studies on the role of angiogenesis and chemokines in inflammatory diseases were carried out in arthritis. However, other systemic inflammatory (autoimmune) diseases including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), polymyositis/dermatomyositis (PM/DM) and systemic vasculites are also discussed in this context. As a number of chemokines may also play a role in neovascularization, this issue is also described here. Apart from discussing the pathogenic role of angiogenesis and chemokines, authors also review the regulation of angiogenesis and chemokine production by other inflammatory mediators, as well as the important relevance of neovascularization and chemokines for antirheumatic intervention.
DNA plasmid production in different host strains of Escherichia coli (2009)

We compared plasmid DNA production in 13 strains of Escherichia coli in shake flasks using media containing glucose or glycerol. DNA yield from either carbon source showed small correlation with maximum growth rate. Three strains, SCS1-L, BL21 and MC4100, were selected for a controlled exponential fed-batch process at a growth rate of 0.14 h(-1) to an optical density of about 70, followed by a four-hour heat treatment. Prior to heat treatment, SCS1-L generated 15.4 mg DNA/g, BL21 generated 11.0 mg DNA/g and MC4100 generated 7.9 mg DNA/g, while after heat treatment the strains attained DNA yields, respectively, of 18.0, 15.0 and 6.8 mg/g. The strains also varied in their percentage of supercoiled DNA after heat treatment, with SCS1-L averaging 66% supercoiled, BL21 17% and MC4100 40%. We further investigated the two strains that yielded the highest percentage of supercoiled DNA (SCS1-L and MC4100) at a higher growth rate of 0.28 h(-1). At this condition, a slightly lower DNA yield was generated faster, and the percentage of supercoiled DNA increased. Heat treatment improved DNA yield, and surprisingly did so to a greater extent at the higher growth rate. As a consequence of these factors, higher growth rates might be advantageous for DNA production.
Identification of protein coding regions in the human genome by quadratic discriminant analysis (1997)

A new method for predicting internal coding exons in genomic DNA sequences has been developed. This method is based on a prediction algorithm that uses the quadratic discriminant function for multivariate statistical pattern recognition. Substantial improvements have been made (with only 9 discriminant variables) when compared with existing methods: HEXON [Solovyev, V. V., Salamov, A. A. & Lawrence, C. B. (1994) Nucleic Acids Res. 22, 5156-5163] (based on linear discriminant analysis) and GRAIL2 [Uberbacher, E. C. & Mural, R. J. (1991) Proc. Natl. Acad. Sci. USA 88, 11261-11265] (based on neural networks). A computer program called MZEF is freely available to the genome community and allows users to adjust prior probability and to output alternative overlapping exons.
Metabolism of Sennosides by Human Intestinal Bacteria (1980)

Species and numbers of intestinal bacteria have recently been investigated and the biochemical interaction between a host and its intestinal flora has become the object of research. It has been suggested that the purgative activities of Rhei rhizoma and Sennae folium are related to the intestinal bacterial action. The present study was undertaken to reveal the process of the metabolism of sennosides, the main effective components of these crude drugs, by human intestinal bacteria, to account for the relation between their defaecation effect and intestinal flora. Through a qualitative study of the ability of 20 species of anaerobes to metabolize sennoside A (A), species were classified into four types: Type I possessing ß-glucosidase activity to produce sennidin, Type II isomerizing A to sennoside B (B), Type III producing unknown glucosides, and Type IV possessing no metabolic activity. Quantitative analyses of intermediates and products clarified the process of the metabolism of A. Type I bacterium, using Clostridium sphenoides as a typical example, reductively cleaved A to produce 8-glucosylrheinanthrone (8GRA), which was then hydrolyzed by ß-glucosidase to produce rheinanthrone (RA), which was rapidly oxidized to sennidin. Type II bacterium, using Eubacte-rium rectale, reduced both A and B to 8GRA in the same way as Type I bacteria, followed by oxidation to the isomers B and A, because of deficiency of ß-glucosidase activity. The active principle is probably RA, which can be formed by Type I bacteria through the reduction and subsequent hydrolysis of sennosides. The individual differences of Type I bacteria in the purgative effect of sennosides may be due to the difference of Type I bacteria in the intestinal flora.
Enhanced Conversion of Triglyceride-Rich Lipoproteins and Increased Low-Density Lipoprotein Removal in LPLS447X Carriers (2005)

Enhanced TRL conversion and enhanced LDL removal combined with increased preheparin LPL concentration suggest increased enzymatic consequences as well as increased nonenzymatic consequences of LPL in LPLS447X carriers, which might both contribute to the cardiovascular benefit of this LPL variant.
ALOHOMORA: a tool for linkage analysis using 10K SNP array data (2005)

ALOHOMORA is available free of charge for non-commercial research institutions. For more details, see http://gmc.mdc-berlin.de/alohomora/
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting (2006)

EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.
A Safe and Noninvasive Test for Vagal Integrity Revisited (2002)

A rise of more than 50% in the PP level within 30 minutes of sham feeding is a strong indicator of vagal integrity. This test has the potential to investigate vagal injury after gastroesophageal surgery.
Gene Expression Profiling and Secretome Analysis Differentiate Adult-Derived Human Liver Stem/Progenitor Cells and Human Hepatic Stellate Cells (2014)

Adult-derived human liver stem/progenitor cells (ADHLSC) are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC) derived from the liver non-parenchymal fraction, present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. ADHLSC and HSC were isolated from the liver of four different donors, expanded in vitro and followed from passage 5 until passage 11. Cell characterization was performed using immunocytochemistry, western blotting, flow cytometry, and gene microarray analyses. The secretion profile of the cells was evaluated using Elisa and multiplex Luminex assays. Both cell types expressed α-smooth muscle actin, vimentin, fibronectin, CD73 and CD90 in accordance with their mesenchymal origin. Microarray analysis revealed significant differences in gene expression profiles. HSC present high expression levels of neuronal markers as well as cytokeratins. Such differences were confirmed using immunocytochemistry and western blotting assays. Furthermore, both cell types displayed distinct secretion profiles as ADHLSC highly secreted cytokines of therapeutic and immuno-modulatory importance, like HGF, interferon-γ and IL-10. Our study demonstrates that ADHLSC and HSC are distinct liver fibroblastic cell populations exhibiting significant different expression and secretion profiles.
Different Species of α-Synuclein Oligomers Induce Calcium Influx and Seeding (2007)

Aggregation of alpha-synuclein (alpha-syn) has been linked to the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases. Increasing evidence suggests that prefibrillar oligomers and protofibrils, rather than mature fibrils of alpha-syn, are the pathogenic species in PD. Despite extensive effort on studying oligomerization of alpha-syn, no studies have compared different oligomer species directly on a single-particle level and investigated their biological effects on cells. In this study, we applied a novel highly sensitive single molecule detection system that allowed a direct comparison of different oligomer types. Furthermore, we studied biological effects of different oligomer types on cells. For this purpose, we developed new oligomerization protocols, that enabled the use of these different oligomers in cell culture. We found that all of our three aggregation protocols resulted in heterogeneous populations of oligomers. Some types of oligomers induced cell death via disruption of cellular ion homeostasis by a presumably pore-forming mechanism. Other oligomer types could directly enter the cell resulting in increased alpha-syn aggregation. Based on our results, we propose that under various physiological conditions, heterogeneous populations of oligomeric forms will coexist in an equilibrium. These different oligomer types lead directly or indirectly to cell damage. Our data indicate that inhibition of early alpha-syn aggregation events would consequently prevent all alpha-syn oligomer related toxicities. This has important implications for the development of disease-modifying drugs for the treatment of PD and other synucleinopathies.
Extracellular nucleotides mediate Ca2+ fluxes in J774 macrophages by two distinct mechanisms. (1988)

We have studied the effects of extracellular nucleotides on the cytosolic free calcium concentration [( Ca2+]i) in J774 macrophages using quin2 and indo-1 as indicator dyes. Micromolar quantities of ATP induced a biphasic increase in [Ca2+]i: a rapid and transient increase (peak I) which was due to mobilization of Ca2+ from intracellular stores and a second more sustained elevation (peak II) due to influx of extracellular Ca2+. The sustained peak II elevation had two components, a "low threshold" (1 microM ATP) response which saturated at 10-50 microM ATP and a "high threshold" response, apparent at [ATP] greater than 100 microM. The latter component was not seen with nucleotides other than ATP and correlated with an ATP-induced generalized increase in plasma membrane permeability. A variant J774 cell line was isolated which does not demonstrate this ATP-induced increase in plasma membrane permeability; nevertheless, it demonstrated both the release of Ca2+ from intracellular stores and the low threshold component of the Ca2+ influx across the plasma membrane in response to nucleoside di- and triphosphates. Several lines of evidence indicate that the fully ionized (i.e. free acid) forms of nucleoside di- and triphosphates were the ligands that mediated these increases in [Ca2+]i. These data show that extracellular nucleotides mediate Ca2+ fluxes by two distinct mechanisms in J774 cells. In one, the rise in [Ca2+]i is due to release of Ca2+ from intracellular stores and Ca2+ influx across the plasma membrane. This response is elicited preferentially by the free acid forms of purine and pyrimidine nucleoside di- and triphosphates. In the other, the rise in [Ca2+]i reflects a more generalized increase in plasma membrane permeability and is elicited by ATP4- only.
New Polymer Syntheses. 78. Star-Shaped and Hyperbranched Polyesters by Polycondensation of Trimethylsilyl 3,5-Diacetoxybenzoate (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Polymer Syntheses. 78. Star-Shaped and Hyperbranched Polyesters by Polycondensation of Trimethylsilyl 3,5-DiacetoxybenzoateHans R. Kricheldorft, Olaf Stoeber, and Dierk LuebbersCite this: Macromolecules 1995, 28, 7, 2118–2123Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ma00111a003https://doi.org/10.1021/ma00111a003research-articleACS PublicationsRequest reuse permissionsArticle Views265Altmetric-Citations57LEARN 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 Get e-Alerts
Characterization of a Human Small‐cell Lung Cancer Cell Line Resistant to a New Water‐soluble Camptothecin Derivative, DX‐8951f (1998)

DX-8951f, a water-soluble and non-pro-drug analogue of camptothecin, exhibits a strong inhibitory action on DNA topoisomerase I (Topo I) and in vitro cytotoxicity against various human cancer cell lines. In order to elucidate the mechanisms of its cytotoxicity, we established a DX-8951f-resistant cell line, SBC-3/DXCL1, from human small cell lung cancer cells (SBC-3) by stepwise exposure to DX-8951f. SBC-3/DXCL1 cells were approximately 400 times more resistant to DX-8951f than parent cells. The SBC-3/DXCL1 cells showed a high degree of cross-resistance to other Topo I inhibitors such as CPT-11, SN-38 and camptothecin, but not to non-Topo I targeting agents such as cisplatin, adriamycin, etoposide, and vincristine. The mechanisms of resistance of SBC-3/DXCL1 cells to DX-8951f were examined. Intracellular accumulation of DX-8951f by SBC-3 and SBC-3/DXCL1 cells did not differ significantly. Although the Topo I activity of nuclear extracts obtained from SBC-3/DXCL1 cells was the same as that of the parent cells, the Topo I of SBC-3/DXCL1 cells was resistant to the inhibitory effects of DX8951f and SN-38. Immunoblotting using anti-Topo I antibody demonstrated similar protein levels of Topo I in SBC-3 and SBC-3/DXCL1 cells. The active Topo I protein of SBC-3/DXCL1 was eluted by a high concentration of NaCl (0.4 N) compared with that of SBC-3 (0.3 N). DX-8951f stabilized the DNA-Topo I cleavable complex from SBC-3 cells, as measured by Topo I-mediated cleavage assay. In SBC-3/DXCL1 cells, DX-8951f also stabilized the DNA-Topo I complex, but with a 10-fold lower efficiency. These results suggest that a qualitative change in Topo I contributes, at least partially, to the resistance to DX-8951f in SBC-3/DXCL1 cells. Therefore, SBC-3/DXCL1 cells may have a unique mechanism of resistance to Topo I-directed antitumor drugs.
Computer diagnosis of supraventricular and ventricular arrhythmias. A new esophageal technique. (1979)

Computerized arrhythmia monitors recognize only a few of the significant arrhythmias and generally fail to detect arrhythmias of supraventricular origin. This is because conventional surface leads, which are sufficient for QRS recognition, are highly inadequate for automated P-wave detection. A new two-lead system, which includes a swallowable capsule-electrode for esophageal monitoring of atrial activity, is used in an on-line arrhythmia monitor. Three interval measurements (AA, AR and RR) and a QRS shape measurement provide the foundation for a detailed interpretation of each beat. Building on the single-beat analysis, a contextual diagnostic algorithm then recognizes and reports on-line the following arrhythmias: couplets, bigeminy, trigeminy, ventricular tachycardia, supraventricular tachycardia, atrial flutter, atrial fibrillation, ventricular tachycardia with retrograde conduction to the atria, first-degree block, second-degree block, Wenckebach periodicity, advanced block, third-degree block and sinus bradycardia.
Accommodation of Misfit Across the Interface Between Crystals of Semiconducting Elements or Compounds (1970)

Misfit dislocations are often transported to the interface between crystals by glide. In materials with the diamond or sphalerite structures, glide is inhibited by the Peierls stress. The aim of this paper is to present a theory for misfit accommodation which includes the effect of the Peierls stress. It is used to explain the elastic strains present in films of germanium on gallium asrenide and to explain the reduction of these strains by a high-temperature anneal. The strains in germanium on gallium arsenide, and the effect of temperature upon them, are not explained by earlier theories for the accommodation of misfit between one crystal and another.
Unsupervised clustering of ambulatory audio and video (1999)

A truly personal and reactive computer system should have access to the same information as its user, including the ambient sights and sounds. To this end, we have developed a system for extracting events and scenes from natural audio/visual input. We find our system can (without any prior labeling of data) cluster the audio/visual data into events, such as passing through doors and crossing the street. Also, we hierarchically cluster these events into scenes and get clusters that correlate with visiting the supermarket, or walking down a busy street.
The ribosomal small‐subunit protein S28 gene from Helianthus annuus (Asteraceae) is down‐regulated in response to drought, high salinity, and abscisic acid (2003)

A partial cDNA for the ribosomal S28 gene from sunflower was initially cloned and identified to be down-regulated by high salinity, using differential display reverse transcriptase-polymerase chain reaction (PCR). Using this sequence, a 502-base pair (bp) full-length cDNA was cloned by rapid amplification of cDNA ends. This cDNA (designated Ha-RPS28) encodes a protein component of the small subunit of cytoplasmic ribosomes. The predicted 65 amino acid residue sequence of Ha-RPS28, with an estimated molecular mass of 7.5 kD, has 92, 89, and 86% identity with the S28 ribosomal proteins from peach, maize, and Arabidopsis, respectively. Ha-RPS28 was expressed in all organs examined, and the highest level was detected in fully expanded leaves. Furthermore, expression of Ha-RPS28 was down-regulated in both seedling roots and shoots in response to drought, high salinity, or abscisic acid.