gebhart/patrepeval huggingface dataset:
Questioning Four Preconceived Ideas on Immunotherapy of Clinical Type 1 Diabetes: Lessons from Recent CD3 Antibody Trials (2005)

The Review of Diabetic Studies,2005,2,3,116-120.DOI:10.1900/RDS.2005.2.116Type:November 2005Authors:Lucienne Chatenoud, and Lucienne Chatenoud Author(s) affiliations:Lucienne Chatenoud and Jean-François Bach Université René Descartes Paris 5, INSERM U580, Hôpital Necker-Enfants Malades, Paris, France. Abstract:Patients presenting type 1 diabetes (T1D) are currently treated with insulin substitutive therapy that is remarkably successful. The treatment has, however, two major limitations that cannot be underestimated due to the major problems and/or discomfort they create, particularly in the numerous patients with unstable metabolic control or insufficient compliance to treatment. The first limitation is degenerative complications that remain an important concern even if their frequency has been dramatically reduced in patients with good metabolic control. The second is the worrisome daily constraints and risks (especially hypoglycemia) linked to regular insulin administration. Several alternatives to palliative insulin therapy have been proposed: pancreas or islet transplantation, β-cell regeneration and immunotherapy. The last strategy, which is in many regards the most straightforward and does not expose patients to the hazards and complications of cell therapy and transplantation, was initiated in the 1980s using cyclosporin in patients presenting newonset T1D[1-3]. Successful remission of disease was obtained with very limited side effects. When the drug was administered at reasonable doses, neither chronic nephrotoxicity nor infections were observed [1-5]. Read more... Keywords:NilView:PDF (312.31 KB)
New signal design for enhanced spatial modulation with multiple constellations (2015)

In this paper, we introduce a new signal design for the Enhanced Spatial Modulation (ESM) concept, which was recently proposed by the present authors. The basic idea of ESM is to convey information bits not only by the indexes of the active transmit antennas, but also by the types of the multiple constellations used. Design of the original ESM schemes involved one or more secondary modulations, which were derived using a single step of geometric interpolation in the signal constellation plane. In the new design, we go one step further in the interpolation process and derive additional modulations leading to a significant increase of the number of active antenna and modulation combinations used. A design example is given for 10 bits per channel use (bpcu) transmission using four transmit antennas two of which are active at a time. The new design is compared to conventional multi-stream spatial modulation (MSM) and to our previously proposed ESM scheme. The analysis and the simulation results confirm a signal-to-noise ratio (SNR) gain of 2.2 dB over MSM and 0.4 dB over ESM when the three schemes are operated at the same spectral efficiency.
Enhanced formation of cubic ice in aqueous organic acid droplets (2008)

The homogeneous nucleation of ice in solution droplets is known to be an important mechanism of ice particle formation in the Earth's upper troposphere. It is known that the metastable cubic phase of ice can form when inorganic solution droplets freeze below about 200 K and that this may influence cloud properties and water vapor in the upper troposphere. However, many tropospheric aerosols contain a large and sometimes dominant proportion of oxygenated organic material in addition to inorganic substances. It is shown here that the threshold freezing temperature below which cubic ice forms and persists is shifted to considerably higher temperatures in solution droplets containing a carboxylic acid (2-hydroxypropane-1,2,3-tricarboxylic acid, citric acid, C6H8O7). Cubic and the stable hexagonal ice are the only phases to crystallize in micrometre sized citric acid droplets and therefore always exist in contact with aqueous citric acid solution. It is argued that the extremely high viscosity of low temperature aqueous citric acid solutions plays an important role in stabilizing cubic ice. The implications of these findings for ice clouds in the Earth's atmosphere are discussed.
Inflammatory response in patients requiring parenteral nutrition: comparison of a new fish-oil-containing emulsion (SMOF®) versus an olive/soybean oil-based formula (2008)

Lipid emulsions are an essential part of parenteral nutrition (PN), such as energy supply and source of essential fatty acids. It has been shown that the composition of cell membranes is influenced by the fatty acid profile of dietary lipids, and may therefore be responsible for modulations in immune response. The aim of this study was to assess the effects of a new lipid emulsion based on soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF®) compared with a lipid emulsion based on olive and soybean oil (ClinOleic®) on the inflammatory response in postoperative ICU patients.
Phosphorylation and Regulation of Raf by Akt (Protein Kinase B) (1999)

Activation of the protein kinase Raf can lead to opposing cellular responses such as proliferation, growth arrest, apoptosis, or differentiation. Akt (protein kinase B), a member of a different signaling pathway that also regulates these responses, interacted with Raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of Raf by Akt inhibited activation of the Raf-MEK-ERK signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt.
Dehydroepiandrosterone Increases Endothelial Cell Proliferationin Vitroand Improves Endothelial Functionin Vivoby Mechanisms Independent of Androgen and Estrogen Receptors (2004)

Dehydroepiandrosterone (DHEA) may be beneficial in cardiovascular health, but mechanisms of DHEA action in the cardiovascular system are unclear. We have therefore 1) determined DHEA effects on the proliferation of cultured endothelial cells (EC), 2) compared effects of DHEA with estradiol (E) and testosterone (T), and 3) examined DHEA effects on subcellular messengers. We have in addition examined effects of DHEA (100 mg/d, 3 months) in 36 healthy postmenopausal women on blood pressure, lipids, and endothelial function, assessed noninvasively in large vessels by flow-mediated dilation of the brachial artery during reactive hyperemia, and in small vessels by laser Doppler velocimetry with iontophoresis of acetylcholine. DHEA, E, and T all increased EC proliferation; the effect of E was abolished by the estrogen receptor antagonist ICI 182,780, and that of T was abolished by the androgen receptor antagonist flutamide; neither blocked the effect of DHEA. In vitro, DHEA increased EC expression of endothelial nitric oxide synthase and activity of extracellular signal-regulated kinase 1/2. In vivo, DHEA increased flow-mediated dilation and laser Doppler velocimetry and reduced total plasma cholesterol. Thus, DHEA increases EC proliferation in vitro by mechanism(s) independently of either androgen receptor or estrogen receptor and in vivo enhances large and small vessel EC function in postmenopausal women.
Interrelationships of scientific journals (1972)

Abstract A series of models of the interrelationship of scientific journals has been developed from the cross citing amongst 275 journals in mathematics, physics, chemistry, biochemistry, and biology. The data source was the Journal Citation Index (JCI), a file derived from the Science Citation Index. The JCI consists of a journal by journal tabulation of citings to and from each journal in the Index. A large amount of consistency was found between the citing characteristics of the journals in the different scientific fields, with quite clear boundaries between fields and a few well known cross disciplinary journals as cross field information links. The separate disciplines appear to relate to each other in an orderly manner, with a natural sequence: mathematics → physics → chemistry → biochemistry → biology. Within disciplines the journals form fully transitive hierarchies with very few relational conflicts.
High-efficiency transformation of Pichia stipitis based on its URA3 gene and a homologous autonomous replication sequence, ARS2 (1994)

This paper describes the first high-efficiency transformation system for the xylose-fermenting yeast Pichia stipitis. The system includes integrating and autonomously replicating plasmids based on the gene for orotidine-5'-phosphate decarboxylase (URA3) and an autonomous replicating sequence (ARS) element (ARS2) isolated from P. stipitis CBS 6054. Ura- auxotrophs were obtained by selecting for resistance to 5-fluoroorotic acid and were identified as ura3 mutants by transformation with P. stipitis URA3. P. stipitis URA3 was cloned by its homology to Saccharomyces cerevisiae URA3, with which it is 69% identical in the coding region. P. stipitis ARS elements were cloned functionally through plasmid rescue. These sequences confer autonomous replication when cloned into vectors bearing the P. stipitis URA3 gene. P. stipitis ARS2 has features similar to those of the consensus ARS of S. cerevisiae and other ARS elements. Circular plasmids bearing the P. stipitis URA3 gene with various amounts of flanking sequences produced 600 to 8,600 Ura+ transformants per micrograms of DNA by electroporation. Most transformants obtained with circular vectors arose without integration of vector sequences. One vector yielded 5,200 to 12,500 Ura+ transformants per micrograms of DNA after it was linearized at various restriction enzyme sites within the P. stipitis URA3 insert. Transformants arising from linearized vectors produced stable integrants, and integration events were site specific for the genomic ura3 in 20% of the transformants examined. Plasmids bearing the P. stipitis URA3 gene and ARS2 element produced more than 30,000 transformants per micrograms of plasmid DNA. Autonomously replicating plasmids were stable for at least 50 generations in selection medium and were present at an average of 10 copies per nucleus.
A New Arenavirus in a Cluster of Fatal Transplant-Associated Diseases (2008)

Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation.
Pain-Related Fear, Lumbar Flexion, and Dynamic EMG Among Persons With Chronic Musculoskeletal Low Back Pain (2004)

Pain-related fear is significantly associated with reduced lumbar flexion, greater EMG in full flexion, and a smaller FRR. The relationship between pain-related fear and EMG during flexion and extension appears to be mediated by reduced lumbar flexion. These results suggest that pain-related fear is directly associated with musculoskeletal abnormalities observed among persons with chronic low back pain, as well as indirectly through limited lumbar flexion. These musculoskeletal abnormalities as well as limited movement may be involved in the development and maintenance of chronic low back pain. In addition, changes in musculoskeletal functioning and flexion associated with pain-related fear may warrant greater attention as part of treatment.
Comparison of FDA safety and efficacy data for KAMRA and Raindrop corneal inlays (2017)

Both devices can be considered safe and effective, however, the results of corneal inlay implantation are mixed, and long-term patient satisfaction will likely depend on subjective expectations about the capabilities of the inlays. Variability in surgical technique and postoperative care within and between the two clinical trials diminishes the comparative power of this article.
The Bcl‐2 family pro‐apoptotic molecule, BNIP3 regulates activation‐induced cell death of effector cytotoxic T lymphocytes (2003)

BNIP3 is a recently described pro-apoptotic member of the Bcl-2 family and in BNIP3 cDNA-transfected cell lines, cell death occurs via a caspase-independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (Delta psi m). However, its expression or function in physiologic cell types is not known. Our results using the T-cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl-2 family pro-apoptotic molecules, BNIP3 is transcriptionally highly up-regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation-induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3-induced cell death. AICD of CTL was caspase-independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3-induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased Delta psi m. Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T-cell homeostasis by regulating effector CTL numbers.
Studies on 3H-Indole. I. General Synthetic Route of 3, 3-Disubstituted 3H-indoles via the Corresponding Oxindoles and then Indolines (1974)

3-Monosubstituted oxindole (4) was converted to 3, 3-disubstituted 1-acetyl-oxindole (1') by acetylation with boiling acetic anhydride followed by alkylation with sodium hydride and alkyl halide in refluxing tetrahydrofuran. The product was saponified in ethanolic potassium hydroxide to 3, 3-disubstituted oxindole (1). 1 was reduced with lithium aluminum hydride or sodium dihydro-bis (2-methoxyethoxy) aluminate to 3, 3-disubstituted indoline (2). To convert the indolines (2) thus obtained to the 3H-indoles (3) ; various oxidizing agents were examined. As a result, dehydrogenation by refluxing with activated manganese dioxide in anhydrous toluene was found to be generally useful for this purpose.
Functional properties of isotype-switched immunoglobulin M (IgM) and IgG monoclonal antibodies to Pseudomonas aeruginosa lipopolysaccharide (1995)

Controversy exists regarding isotype-related differences in the antibacterial and protective properties of lipopolysaccharide (LPS)-specific antibodies of the immunoglobulin M (IgM) class and various IgG subclasses. To clarify this issue, a murine hybridoma secreting IgM monoclonal antibody (MAb) specific for the O polysaccharide of Pseudomonas aeruginosa serogroup O6 LPS was class switched, by sib selection, to produce an IgG3 MAb with identical specificity and variable region heavy and light chain nucleotide sequences. This IgG3-secreting cell line was further switched to the production of O-specific, variable region-identical IgG1, IgG2b, and IgG2a MAbs. Functional comparisons of these LPS-specific IgM and IgG MAb isotypes revealed similar LPS binding, opsonic, and protective activities. Relatively minor isotype-related differences in levels of efficiency of MAb-mediated, complement-dependent opsonophagocytic killing (IgM > IgG2a > IgG3 > IgG2b > > IgG1) were not associated with corresponding differences in in vivo functions. These findings, in conjunction with previously published data, support a cautious approach to generic conclusions regarding the immunotherapeutic superiority of LPS-specific antibodies belonging to either the IgM or IgG class or to a particular IgG subclass.
Mutations that affect production of branched RNA-linked msDNA in Myxococcus xanthus (1988)

A deletion mutation of the gene (msd-msr) for the branched RNA-linked msDNA of Myxococcus xanthus was constructed by replacing the chromosomal 0.7-kilobase (kb) SmaI-XhoI fragment encompassing msd-msr with a 1.4-kb fragment carrying a gene for kanamycin resistance. It was found that this deletion strain (delta msSX) could not produce msDNA, although it still contained another species of msDNA, mrDNA (msDNA, reduced size). No apparent differences between delta msSX and the wild-type strain were observed in terms of cell growth, morphogenesis, fruiting-body formation, or motility. Both a deletion mutation at the region 100 base pairs upstream of msd and an insertion mutation at a site 500 base pairs upstream of msd showed a significant reduction of msDNA production, indicating that there is a cis- or trans-acting positive element in this region. When the 3.5-kb BamHI fragment carrying msd-msr from Stigmatella aurantiaca was inserted into the M. xanthus chromosome, the S. aurantiaca msDNA was found to be produced in M. xanthus.
Activities of newly synthesized dihydropyridines in overcoming of vincristine resistance, calcium antagonism, and inhibition of photoaffinity labeling of P-glycoprotein in rodents. (1990)

Newly synthesized 1,4-dihydropyridine derivatives (NK-compounds) were screened to determine whether they could overcome vincristine (VCR) resistance in VCR-resistant (P388/VCR) leukemia-bearing mice. Among the 57 NK-compounds examined, six compounds had strong reversing ability (Grade A), 18 partially overcame the resistance (Grade B), and 33 did not reverse the resistance (Grade C). The ability to overcome resistance varied considerably with the nature of substituents at positions 3.5 of the 1,4-dihydropyridine, and the most suitable substituents were the pyridylalkyl-including esters. Calcium antagonistic activity of NK-compounds having pyridylalkyl-including esters at positions 3.5 and dithiene ring at position 4 of the 1,4-dihydropyridine was greater than in those compounds having the dioxene ring at position 4. NK-242, which was assessed at Grade A and had no calcium antagonistic activity, improved therapeutic effects in both VCR-sensitive (P388/S) leukemia- and P388/VCR leukemia-bearing mice when combined with VCR. Fourteen NK-compounds were screened to determine whether they could inhibit photoaffinity labeling of the P-glycoprotein (Mr 170,000 glycoprotein) in a multidrug-resistant cell line by [3H]azidopine. All six compounds of Grade A and two of the three compounds of Grade B almost completely inhibited the labeling of Mr 170,000 glycoprotein at 1 to 10 microM. Thus there was a good correlation between the ability to reverse VCR resistance in vivo and the inhibition of photoaffinity labeling of Mr 170,000 glycoprotein.
Safety and Immunogenicity of a Vi Polysaccharide–Tetanus Toxoid Conjugate Vaccine (Typbar-TCV) in Healthy Infants, Children, and Adults in Typhoid Endemic Areas: A Multicenter, 2-Cohort, Open-Label, Double-Blind, Randomized Controlled Phase 3 Study (2015)

CTRI/2011/08/001957, CTRI/2014/01/004341.
Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120. (1988)

The major envelope glycoprotein, gp120, of human immunodeficiency virus type 1 (HIV-1) was purified from a Chinese hamster ovary cell line transfected with a truncated form of the HIV-1 env gene. The recombinant glycoprotein (rgp120) was formulated with aluminum hydroxide adjuvant and was used to immunize chimpanzees. The recombinant preparation was effective in eliciting cellular and humoral immunity as well as immunologic memory. Anti-rgp 120 antibodies reacted with authentic viral gp120 in immunological blot assays and were able to neutralize HIV-1 infectivity in vitro. Sera from the rgp120-immunized animals were able to neutralize HIV-1 pseudotypes of vesicular stomatitis virus prepared from the IIIB isolate, from which the gene encoding rgp120 was derived, as well as two heterologous isolates, ARV-2 and RF. The immune response elicited against the rgp120 was not effective in preventing viral infection after intravenous challenge with HIV-1. The implications of these results on HIV-1 vaccine development are discussed.
A peroxidase-coupled method for the colorimetric determination of serum triglycerides. (1983)

Abstract We describe an enzymatic method for rapid, precise measurement of serum triglycerides with use of sample:reagent ratios as large as 1:200. Hydrolysis of triglycerides is catalyzed by lipase to produce glycerol and free fatty acids. The glycerol generated is then phosphorylated by adenosine 5'-triphosphate in the presence of glycerol kinase. Oxidation of the resulting glycerol 3-phosphate to produce hydrogen peroxide is catalyzed by L-alpha-glycerophosphate oxidase. An intense red chromogen is produced by the peroxidase-catalyzed coupling of 4-aminoantipyrene and sodium 2-hydroxy-3,5-dichlorobenzenesulfonate with hydrogen peroxide. This sensitive chromogen system not only permits use of unusually small sample volumes, it also facilitates a linear response to serum triglyceride concentrations up to at least 10 g/L while displaying good Ringbom (measure of accuracy) characteristics.
Drug Delivery from Bioerodible Polymers (1994)

The recent progress in understanding the erosion of biodegradable polymers and the manufacturing of controlled release devices for proteins and peptides is reported. The erosion mechanism of poly(anhydrides) was investigated as an example of biodegradable polymers and the erosion behavior is modeled mathematically. The results provide useful information on the microstructure and chemical environment inside these polymers during erosion. It is shown how they might affect the stability and the release of proteins. Concomitantly proteins were processed in controlled release devices. Special attention was paid to the stability of the biomolecules during the manufacturing of dosage forms. Furthermore, the development of a new type of biodegradable nanosphere as a future dosage form is shown.
Assembly of anthrax toxin pore: Lethal‐factor complexes into lipid nanodiscs (2013)

We have devised a procedure to incorporate the anthrax protective antigen (PA) pore complexed with the N-terminal domain of anthrax lethal factor (LFN ) into lipid nanodiscs and analyzed the resulting complexes by negative-stain electron microscopy. Insertion into nanodiscs was performed without relying on primary and secondary detergent screens. The preparations were relatively pure, and the percentage of PA pore inserted into nanodiscs on EM grids was high (∼43%). Three-dimensional analysis of negatively stained single particles revealed the LFN -PA nanodisc complex mirroring the previous unliganded PA pore nanodisc structure, but with additional protein density consistent with multiple bound LFN molecules on the PA cap region. The assembly procedure will facilitate collection of higher resolution cryo-EM LFN -PA nanodisc structures and use of advanced automated particle selection methods.