gebhart/patrepeval huggingface dataset:
Préparation et caractérisation de polymères-modèle à structure en étoile, par copolymérisation séquencée anionique (1969)

Star-shaped polystyrene samples have been synthesized by anionic block-copolymerization of styrene and divinylbenzene (DVB), the proportion of the latter monomer being of the order of a few molecules per living end. Vacuum technique was used and benzene was chosen as solvent. The samples were found almost free of linear polystyrene, and of very low polydispersity. The number of branches was found to be a function of the overall concentration, of the amount of DVB, and of the molecular weight of the linear precursor. The results obtained with the meta and the para isomers did not differ significantly, as far as the products themselves are concerned. However, spectroscopic investigations carried out during reaction showed that the reactivity of the 2 double bonds of the para isomer differ significantly, whereas this is not the case with the meta isomer.
Cloning and Characterization of a cDNA Encoding .BETA.-Amyrin Synthase Involved in Glycyrrhizin and Soyasaponin Biosyntheses in Licorice. (2001)

An oxidosqualene cyclase cDNA, termed GgbAS1, was isolated from cultured cells of licorice (Glycyrrhiza glabra) by heterologous hybridization with cDNA of Arabidopsis thaliana LUP1 lupeol synthase. The yeast transformed with an expression vector containing the open reading frame of GgbAS1 produced beta-amyrin, indicating that GgbAS1 encodes beta-amyrin synthase involved in the glycyrrhizin and soyasaponin biosyntheses in licorice. Northern blot analysis showed that the level of beta-amyrin synthase mRNA was drastically changed in the cultured licorice cells, whereas the mRNA level of cycloartenol synthase was relatively constant.
Development and evaluation of an efficient cell-culture system for Hepatitis E virus (2007)

Using a faecal suspension with high load of Hepatitis E virus (HEV) (2.0x10(7) copies ml-1, genotype 3), we developed an efficient cell-culture system for HEV in a hepatocarcinoma cell line (PLC/PRF/5). HEV progeny released in the culture medium were passaged five times successively in PLC/PRF/5 cells. The initial day of appearance and load of HEV detectable in the culture supernatant after inoculation were dependent on the titre of seed virus in the inoculum. When 6.4x10(4) copies of HEV were inoculated on monolayers of PLC/PRF/5 cells in six-well microplates, HEV RNA was first detected in the culture medium on day 14 post-inoculation and increased to 9.1x10(5) copies ml-1 on day 60. When 8.6x10(5) copies of HEV were inoculated, HEV RNA was initially detected on day 12 and reached the highest titre of 8.6x10(7) copies ml-1 on day 60. HEV incubated at temperatures higher than 70 degrees C did not grow in PLC/PRF/5 cells, while HEV incubated at 56 degrees C for 30 min was infectious. Convalescent serum samples with IgM-class HEV antibodies obtained from patients infected with HEV of genotype 1, 3 or 4 neutralized the genotype 3 virus, indicating that HEV antibodies are broadly cross-reactive. Serum samples obtained from patients 8.7 or 24.0 years after the onset of HEV infection also prevented the propagation of HEV in PLC/PRF/5 cells, suggesting the presence of long-lasting HEV antibodies with neutralizing activity in individuals with past HEV infection.
Lipoprotein from the osmoregulated ABC transport system OpuA of Bacillus subtilis: purification of the glycine betaine binding protein and characterization of a functional lipidless mutant (1997)

The OpuA transport system of Bacillus subtilis functions as a high-affinity uptake system for the osmoprotectant glycine betaine. It is a member of the ABC transporter superfamily and consists of an ATPase (OpuAA), an integral membrane protein (OpuAB), and a hydrophilic polypeptide (OpuAC) that shows the signature sequence of lipoproteins (B. Kempf and E. Bremer, J. Biol. Chem. 270:16701-16713, 1995). The OpuAC protein might thus serve as an extracellular substrate binding protein anchored in the cytoplasmic membrane via a lipid modification at an amino-terminal cysteine residue. A malE-opuAC hybrid gene was constructed and used to purify a lipidless OpuAC protein. The purified protein bound radiolabeled glycine betaine avidly and exhibited a KD of 6 microM for this ligand, demonstrating that OpuAC indeed functions as the substrate binding protein for the B. subtilis OpuA system. We have selectively expressed the opuAC gene under T7 phi10 control in Escherichia coli and have demonstrated through its metabolic labeling with [3H]palmitic acid that OpuAC is a lipoprotein. A mutant expressing an OpuAC protein in which the amino-terminal cysteine residue was changed to an alanine (OpuAC-3) was constructed by oligonucleotide site-directed mutagenesis. The OpuAC-3 protein was not acylated by [3H]palmitic acid, and part of it was secreted into the periplasmic space of E. coli, where it could be released from the cells by cold osmotic shock. The opuAC-3 mutation was recombined into an otherwise wild-type opuA operon in the chromosome of B. subtilis. Unexpectedly, this mutant OpuAC system still functioned efficiently for glycine betaine acquisition in vivo under high-osmolarity growth conditions. In addition, the mutant OpuA transporter exhibited kinetic parameters similar to that of the wild-type system. Our data suggest that the lipidless OpuAC-3 protein is held in the cytoplasmic membrane of B. subtilis via its uncleaved hydrophobic signal peptide.
Management of the patient with eosinophilic asthma: a new era begins (2015)

Now that it is generally accepted that asthma is a heterogeneous condition, phenotyping of asthma patients has become a mandatory part of the diagnostic workup of all patients who do not respond satisfactorily to standard therapy with inhaled corticosteroids. Late-onset eosinophilic asthma is currently one of the most well-defined asthma phenotypes and seems to have a different underlying pathobiology to classical childhood-onset, allergic asthma. Patients with this phenotype can be identified in the clinic by typical symptoms (few allergies and dyspnoea on exertion), typical lung function abnormalities ("fixed" airflow obstruction, reduced forced vital capacity and increased residual volume), typical comorbidities (nasal polyposis) and a good response to systemic corticosteroids. The definitive diagnosis is based on evidence of eosinophilia in bronchial biopsies or induced sputum, which can be estimated with reasonable accuracy by eosinophilia in peripheral blood. Until recently, patients with eosinophilic asthma had a very poor quality of life and many suffered from frequent severe exacerbations or were dependent on oral corticosteroids. Now, for the first time, novel biologicals targeting the eosinophil have become available that have been shown to be able to provide full control of this type of refractory asthma, and to become a safe and efficacious substitute for oral corticosteroids.
Increased Immunogenicity of a DNA-Launched Venezuelan Equine Encephalitis Virus-Based Replicon DNA Vaccine (2007)

A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). The VEE DNA consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional DNA vaccine. Furthermore, transfection with the DNA-launched VEE replicon induced apoptosis and type I interferon production. Inoculation of mice with VEE DNA encoding human immunodeficiency virus type 1 gp160 significantly increased humoral responses by several orders of magnitude compared to an equal dose of a conventional DNA vaccine. These increases were also observed at 10- and 100-fold-lower doses of the VEE DNA. Cellular immune responses measured by gamma interferon and interleukin 2 enzyme-linked immunospot assay were significantly higher in mice immunized with the VEE DNA at decreased doses. The immune responses induced by the VEE DNA-encoded antigen, however, were independent of an intact type I interferon signaling pathway. Moreover, the DNA-launched VEE replicon induced an efficient prime to a VEE replicon particle (VRP) boost, increasing humoral and cellular immunity by at least 1 order of magnitude compared to VEE DNA only. Importantly, immunization with VEE DNA, as opposed to VRP, did not induce any anti-VRP neutralizing antibodies. Increased potency of DNA vaccines and reduced vector immunity may ultimately have an impact on the design of vaccination strategies in humans.
Synthesis of hepatitis B surface antigen in mammalian cells: expression of the entire gene and the coding region (1983)

We have constructed two simian virus 40 early replacement recombinants that have the coding sequences for hepatitis B virus surface antigen (HBsAg). One construction, LSV-HBsAg, has the coding region for HBsAg but not the portion encoding the putative pre-surface antigen leader. Transformed monkey kidney cells (COS) infected with this recombinant express large quantities of the characteristic partially glycosylated HBsAg molecule, which are assembled into 22-nm particles that appear similar to those produced by human liver cells infected with hepatitis B virus. This result indicates that the pre-surface antigen sequences are not required for the synthesis of HBsAg or its assembly into particulate structures. The second recombinant, LSV-HBpresAg, has the entire surface antigen gene, including the putative promoter and pre-surface antigen region. COS cells infected with this recombinant plasmid produce 40- to 50-fold less HBsAg than those infected with the LSV-HBsAg recombinant plasmid. RNA mapping studies suggest that the transcription of the HBsAg gene is initiated at more than one site, or alternatively, that RNA splicing of transcripts occurs in the pre-surface antigen region.
Depth scanning for a conformal ion beam treatment of deep seated tumours (2000)

Only target-conformal treatment allows one to exploit the advantages of ion beams (the increased dose and high biological efficiency at the end of the particle range) to a maximum extent. Up to now, target-conformal treatments such as spot scanning or intensity-controlled raster scanning have used fast magnetic lateral deflection in one or two directions perpendicular to the beam axis and a slow range variation in the longitudinal axis by active or passive energy variation. The present paper describes a new method for conformal irradiation with a fast intensity-controlled longitudinal scan in the beam direction, called 'depth scanning'. Its advantages and disadvantages will be discussed. First experimental results from depth scanning will be presented.
Salmonella Promoters Preferentially Activated Inside Tumors (2008)

Salmonella enterica and avirulent derivatives prefer solid tumors over normal tissue in animal models. The identification of endogenous Salmonella promoters that are preferentially activated in tumors could further our understanding of this phenomenon. Toward this goal, a random library of S. enterica typhimurium 14028 genomic DNA was cloned upstream of a promoterless gene encoding the green fluorescent protein (GFP) TurboGFP. A population of Salmonella containing this library was injected i.v. into tumor-free nude mice and into human PC3 prostate tumors growing subcutaneously in nude mice. After 2 days, fluorescence-activated cell sorting was used to enrich for bacterial clones expressing GFP from spleens or tumors. The resulting libraries were hybridized to an oligonucleotide tiling array of the Salmonella genome. Eighty-six intergenic regions were found to be enriched in tumor samples but not in spleen. Twenty of these candidate promoters were also detected in the sequences of 100 random clones from a library enriched for expression in bacteria growing in tumors. Three candidate promoter clones were individually tested in vivo, and enhanced GFP expression in bacteria growing in tumor relative to spleen was confirmed. Two of the three clones (pflE and ansB promoter regions) are known to be induced in hypoxic conditions that pertain to many tumors. For many of the other candidate promoters preferentially induced in bacteria growing in tumors, regulatory mechanisms may not be related to hypoxia. The expression of therapeutics in Salmonella under the regulation of one or more promoters that are activated preferentially in tumors has the potential to improve the targeting of drug delivery.
A String of Enzymes, Purification and Characterization of a Fusion Protein Comprising the Four Subunits of the Glucose Phosphotransferase System of Escherichia coli (1995)

A multidomain protein comprising the four subunits of the glucose phosphotransferase system of Escherichia coli was constructed by fusion of the transmembrane subunit IICBGlc and the three cytoplasmic proteins, IIAGlc, HPr, and enzyme I. The subunits were linked in the above order with Ala-Pro-rich linkers; the fusion protein was overexpressed in E. coli and purified by Ni2+ chelate affinity chromatography. Approximately 3 mg of the fusion protein could be purified from 1 liter of culture. The phosphotransferase activity of the purified fusion protein was 3-4 times higher than that of an equimolar mixture of the isolated subunits. The mannose transporter, which also requires enzyme I and HPr, was not an effective competitor in the overall phosphoryltransfer reaction when the fusion protein was used, whereas it was a competitor when an equimolar mixture of the separate subunits was employed. Transphosphorylation activity of the fusion protein was almost indistinguishable from the wild-type IICBglc. Addition of extra IICBGlc subunit could significantly stimulate the phosphotransferase activity of the fusion protein, addition of extra IIAGlc subunit and enzyme I, in contrast, was slightly inhibitory, and HPr had almost no effect. An optimal detergent-lipid ratio is required for maximum activity of the fusion protein. Our results suggest that Ala-Pro-rich linker sequences may be of general use for the construction of catalytically active fusion proteins with novel properties.
A graph‐theory algorithm for rapid protein side‐chain prediction (2003)

Fast and accurate side-chain conformation prediction is important for homology modeling, ab initio protein structure prediction, and protein design applications. Many methods have been presented, although only a few computer programs are publicly available. The SCWRL program is one such method and is widely used because of its speed, accuracy, and ease of use. A new algorithm for SCWRL is presented that uses results from graph theory to solve the combinatorial problem encountered in the side-chain prediction problem. In this method, side chains are represented as vertices in an undirected graph. Any two residues that have rotamers with nonzero interaction energies are considered to have an edge in the graph. The resulting graph can be partitioned into connected subgraphs with no edges between them. These subgraphs can in turn be broken into biconnected components, which are graphs that cannot be disconnected by removal of a single vertex. The combinatorial problem is reduced to finding the minimum energy of these small biconnected components and combining the results to identify the global minimum energy conformation. This algorithm is able to complete predictions on a set of 180 proteins with 34342 side chains in <7 min of computer time. The total chi(1) and chi(1 + 2) dihedral angle accuracies are 82.6% and 73.7% using a simple energy function based on the backbone-dependent rotamer library and a linear repulsive steric energy. The new algorithm will allow for use of SCWRL in more demanding applications such as sequence design and ab initio structure prediction, as well addition of a more complex energy function and conformational flexibility, leading to increased accuracy.
Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. (1993)

The hypertriglyceridemia of infection was traditionally thought to represent the mobilization of substrate to fuel the body's response to the infectious challenge. However, we have previously shown that triglyceride-rich lipoproteins can protect against endotoxin-induced lethality. The current studies examine the mechanism by which this protection occurs. Rats infused with a lethal dose of endotoxin preincubated with chylomicrons had a reduced mortality compared with rats infused with endotoxin alone (15 vs. 76%, P < 0.001). Preincubation with chylomicrons increased the rate of clearance of endotoxin from plasma and doubled the amount of endotoxin cleared by the liver (30 +/- 1 vs. 14 +/- 2% of the total infused radiolabel, P < 0.001). In addition, autoradiographic studies showed that chylomicrons directed more of the endotoxin to hepatocytes and away from hepatic macrophages. Rats infused with endotoxin plus chylomicrons also showed reduced peak serum levels of tumor necrosis factor as compared with controls (14.2 +/- 3.3 vs. 44.9 +/- 9.5 ng/ml, mean +/- SEM, P = 0.014). In separate experiments, chylomicrons (1,000 mg triglyceride/kg) or saline were infused 10 min before the infusion of endotoxin. Chylomicron pretreatment resulted in a reduced mortality compared with rats infused with endotoxin alone (22 vs. 78%, P < 0.005). Therefore, chylomicrons can protect against endotoxin-induced lethality with and without preincubation with endotoxin. The mechanism by which chylomicrons protect against endotoxin appears to involve the shunting of endotoxin to hepatocytes and away from macrophages, thereby decreasing macrophage activation and the secretion of cytokines.
Microscope-Integrated Quantitative Analysis of Intraoperative Indocyanine Green Fluorescence Angiography for Blood Flow Assessment (2011)

Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.
Correlations between insulin antibodies and the HLA system in a group of type I diabetic patients in Bucharest. (1986)

Investigations were carried out in Bucharest in 102 patients with insulin-dependent diabetes mellitus (IDDM) in order to verify the possible existence of a relationship between the HLA system and the level of insulin antibodies. The A and B loci were tested with monospecific antisera, using PEC as a separation agent for the determination of the insulin antibody titer. Group I, without antibodies (34 cases), presented: HLA-B7 (18.89% of total specificities), A3 (11.02%), A1 and B5 (8.74% each), etc.: for haplotypes the following were found: HLA-A3/B7 (9.91% of the total haplotypes), A2/B7 (8.26%), A1/B7 (5.78%). Group II (50 cases) with low or medium titers (less than 30% binding) included: HLA-B7 (20.47%), A2 (11.88%), (A1 (9.44%), B5 (8.74%), and haplotypes: HLA-A2/B7 (8.88%), A1/B7 (7.22%), A3/B7 (6.11%). Group III (18 cases), with high antibody titers (greater than 30% binding), presented: HLA-B7 (20.28%), A1 and A2 (11.59% each), A10 (10.14%), and haplotypes: HLA-A1/B7 (10.60%), A2/B7 and A10/B7 (9.09% each), A3 B7, A2 B5 and A10/B5, (6.06% each). Irrespective of the insulin antibody titer, B7 antigen surprisingly appeared predominant in our cases. Moreover, a marked tendency of A1, and to a certain extent of A2, to increase in terms of the titer was noted in parallel with a significant decrease of A3.
The Role of Hemopoietic Growth Factors in Self-Renewal and Differentiation of IL-3-Dependent Multipotential Stem Cells (1990)

A multipotent hemopoietic cell line has been employed to assess the influence of the hemopoietic growth factors, IL-3, GM-CSF, G-CSF, and CSF-1 on the processes of self-renewal, the generation of lineage restricted progenitor cells and the production of mature neutrophils and macrophages. At a high concentration of IL-3, the cells undergo self-renewal and demonstrate little or no ability to undergo differentiation in the presence of the other growth factors. In the absence of IL-3, the cells show minimal (GM-CSF) or no (G-CSF or CSF-1) ability to respond to these other growth factors. When combined with a low concentration of IL-3, the ability of the cells to respond to GM-CSF, G-CSF, and CSF-1 is enhanced and a selective preference for the neutrophil or macrophage lineage is seen depending on the combination used, i.e., the presence of CSF-1 preferentially promotes macrophage development and G-CSF preferentially promotes neutrophil development. Conditions optimal for neutrophil development were seen using a combination of low IL-3 concentrations plus GM-CSF plus G-CSF. In such conditions, the cells undergo extensive proliferation and progressively lose their clonogenic potential (i.e., differentiation much greater than self-renewal) and acquire the biochemical markers characteristic of fully mature phagocytes.
Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer (2017)

Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399 .).
Disseminated Fusarium infections in patients following bone marrow transplantation. (1989)

Intensive immunosuppressive therapy and broad spectrum antibiotics predispose cancer patients to opportunistic fungal infections. Fusarium has rarely been reported as a pathogen in immunocompromised patients, but is almost uniformly fatal. Only six cases of disseminated Fusarium infection have been described in patients following bone marrow transplantation (BMT). We report here two additional cases. Fusarium infection initially presented with pyomyositis in one patient and with embolic skin lesions in another following T cell-depleted BMT. Both patients died with active Fusarium infection despite an extensive course of amphotericin B, rifampicin and granulocyte transfusions. From this experience and from a review of the literature, Fusarium infections appear to be increasing in prevalence as significant pathogens in immunocompromised hosts and are resistant to many conventional forms of therapy.