gebhart/patrepeval huggingface dataset:
Dose‐response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS) (1995)

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse. The bovine and the Recombinant LSF are superior to both synthetic LSFpreparations.5. In this animal model and under the described specific ventilatory settings, even between bovine LSFpreparations there are detectable differences that are pronounced when compared to synthetic LSFwithout any surfactant proteins. We conclude that the difference between bovine and synthetic LSFpreparations can be overcome by addition of the surfactant protein C.
Serine/Threonine Kinases 3pK and MAPK-activated Protein Kinase 2 Interact with the Basic Helix-Loop-Helix Transcription Factor E47 and Repress Its Transcriptional Activity (2000)

In the search for physiological substrates of MAPK-activated protein (MAPKAP) kinases, we identified the basic helix-loop-helix (bHLH) transcription factor E47 as an interaction partner of chromosome 3p kinase (3pK) and MAPKAP-K2 (MK2). The E2A protein E47 is known to be involved in the regulation of tissue-specific gene expression and cell differentiation. E47 is a phosphoprotein, and we identified 3pK and MK2 as E47 kinases in vitro. Furthermore, the expression of either kinase results in a repression of the transcriptional activity of E47 on an E-box containing promoter. In summary, the MAPK-activated protein kinases 3pK and MK2 were identified to form an assembly with the bHLH protein E47 suggesting that these kinases are regulators of E47 activity and E47-dependent gene expression.
Quantitative Vibrational Imaging by Hyperspectral Stimulated Raman Scattering Microscopy and Multivariate Curve Resolution Analysis (2012)

Spectroscopic imaging has been an increasingly critical approach for unveiling specific molecules in biological environments. Toward this goal, we demonstrate hyperspectral stimulated Raman loss (SRL) imaging by intrapulse spectral scanning through a femtosecond pulse shaper. The hyperspectral stack of SRL images is further analyzed by a multivariate curve resolution (MCR) method to reconstruct quantitative concentration images for each individual component and retrieve the corresponding vibrational Raman spectra. Using these methods, we demonstrate quantitative mapping of dimethyl sulfoxide concentration in aqueous solutions and in fat tissue. Moreover, MCR is performed on SRL images of breast cancer cells to generate maps of principal chemical components along with their respective vibrational spectra. These results show the great capability and potential of hyperspectral SRL microscopy for quantitative imaging of complicated biomolecule mixtures through resolving overlapped Raman bands.
Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling (2015)

In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this has proven more challenging due to technical aspects. To provide a flexible and effective method for investigating somatic loss-of-function alterations and their influence on tumorigenesis, we have established CRISPR/Cas9-mediated somatic gene disruption, allowing for in vivo targeting of TSGs. Here we demonstrate the utility of this approach by deleting single (Ptch1) or multiple genes (Trp53, Pten, Nf1) in the mouse brain, resulting in the development of medulloblastoma and glioblastoma, respectively. Using whole-genome sequencing (WGS) we characterized the medulloblastoma-driving Ptch1 deletions in detail and show that no off-targets were detected in these tumours. This method provides a fast and convenient system for validating the emerging wealth of novel candidate tumour suppressor genes and the generation of faithful animal models of human cancer.
Phosphatidyl inositol 3' kinase-independent p70 S6 kinase activation by FGF receptor-1 is important for proliferation but not differentiation of endothelial cells. (1997)

Phosphatidyl inositol 3' kinase-independent p70 S6 kinase activation by FGF receptor-1 is important for proliferation but not differentiation of endothelial cells.
Neuroprotective role of bradykinin because of the attenuation of pro‐inflammatory cytokine release from activated microglia (2006)

Abstract Bradykinin (BK) has been reported to be a mediator of brain damage in acute insults. Receptors for BK have been identified on microglia, the pathologic sensors of the brain. Here, we report that BK attenuated lipopolysaccharide (LPS)‐induced release of tumor necrosis factor‐alpha (TNF‐α) and interleukin‐1β from microglial cells, thus acting as an anti‐inflammatory mediator in the brain. This effect was mimicked by raising intracellular cAMP or stimulating the prostanoid receptors EP2 and EP4, while it was abolished by a cAMP antagonist, a prostanoid receptor antagonist, or by an inhibitor of the inducible cyclooxygenase (cyclooxygenase‐2). BK also enhanced formation of prostaglandin E 2 and expression of microsomal prostaglandin E synthase. Expression of BK receptors and EP2/EP4 receptors were also enhanced. Using physiological techniques, we identified functional BK receptors not only in culture, but also in microglia from acute brain slices. BK reduced LPS‐induced neuronal death in neuron–microglia co‐cultures. This was probably mediated via microglia as it did not affect TNF‐α‐induced neuronal death in pure neuronal cultures. Our data imply that BK has anti‐inflammatory and neuroprotective effects in the central nervous system by modulating microglial function.
The Human Amygdala: An Evolved System for Relevance Detection (2003)

Evidence from pioneering animal research has suggested that the amygdala is involved in the processing of aversive stimuli, particularly fear-related information. Fear is central in the evolution of the mammalian brain: it is automatically and rapidly elicited by potentially dangerous and deadly events. The view that the amygdala shares the main characteristics of modular systems, e.g. domain specificity, automaticity, and cognitive impenetrability, has become popular in neuroscience. Because of its computational properties, it has been proposed to implement a rapid-response 'fear module'. In this article, we review recent patient and neuroimaging data of the human brain and argue that the fundamental criteria for the amygdala to be a modular system are not met. We propose a different computational view and suggest the notion of a specific involvement of the human amygdala in the appraisal of relevant events that include, but are not restricted to, fear-related stimuli. Considering the amygdala as a 'relevance detector' would integrate the 'fear module' hypothesis with the concept of an evolved neural system devoted to the processing of a broader category of biologically relevant stimuli. In primates, socially relevant events appear to have become, through evolution, the dominant elements of the amygdala's domain of specificity.
Implementation considerations for Mobile IP (2002)

The Mobile IP protocol allows transparent routing of IP datagrams on the Internet. Each mobile node is identified by its home address disregarding its current location in the Internet. While away from home, a mobile node is associated with a care-of address which gives information about its current location. Mobile IP specifies how a mobile node registers with its home agent and how the home agent routes datagrams to the mobile node through a tunnel. The authors first outline the Mobile IP protocol and its extension mechanism defined for carrying information. They then present the architecture of their working implementation which is based on objected-oriented methodology. Finally some implementation considerations and challenges for Mobile IP are investigated.
Clinical use of blade atrial septostomy. (1978)

A cardiac catheter enclosing an extensible blade was used to enlarge the interatrial opening in seven patients. Two patients with transposition of the great arteries who had balloon atrial septostomy as newborns subsequently presented with clinical evidence of a restrictive interatrial opening at 1 and 4 months of age. Cardiac catheterization confirmed restenosis of the interatrial opening and inadequate intracardiac mixing. After blade atrial septostomy the systemic arterial oxygen saturation increased by 20% and 30%, respectively. Five patients with mitral atresia complex, ages 2 months-9 1/2 years, had a restrictive interatrial communication and severe pulmonary venous hypertension (mean left atrial pressures ranged from 20-38 mm Hg). Following blade atrial septostomy, the pressure gradient between the atria was almost completely abolished and prompt clinical improvement was observed in each patient. All patients tolerated the procedure without complications. Blade atrial septostomy was a safe, effective procedure for enlarging the interatrial communication in this limited series of patients with an interatrial septum too thick to permit adequate rupture by conventional balloon atrial septostomy.
High-efficiency gene inactivation and replacement system for gram-positive bacteria (1993)

A system for high-efficiency single- and double-crossover homologous integration in gram-positive bacteria has been developed, with Lactococcus lactis as a model system. The system is based on a thermosensitive broad-host-range rolling-circle plasmid, pG+host5, which contains a pBR322 replicon for propagation in Escherichia coli at 37 degrees C. A nested set of L. lactis chromosomal fragments cloned onto pG+host5 were used to show that the single-crossover integration frequency was logarithmically proportional to the length of homology for DNA fragments between 0.35 and 2.5 kb. Using random chromosomal 1-kb fragments, we showed that homologous integration can occur along the entire chromosome. We made use of the reported stimulatory effect of rolling-circle replication on intramolecular recombination to develop a protocol for gene replacement. Cultures were first maintained at 37 degrees C to select for a bacterial population enriched for plasmid integrants; activation of the integrated rolling-circle plasmid by a temperature shift to 28 degrees C resulted in efficient plasmid excision by homologous recombination and replacement of a chromosomal gene by the plasmid-carried modified copy. More than 50% of cells underwent replacement recombination when selection was applied for the replacing gene. Between 1 and 40% of cells underwent replacement recombination when no selection was applied. Chromosomal insertions and deletions were obtained in this way. These results show that gene replacement can be obtained at an extremely high efficiency by making use of the thermosensitive rolling-circle nature of the delivery vector. This procedure is applicable to numerous gram-positive bacteria.
Inhibition of Serotonin 5-Hydroxytryptamine2C Receptor Function through Heterodimerization (2005)

Although dimerization appears to be a common property of G-protein-coupled receptors (GPCRs), it remains unclear whether a GPCR dimer binds one or two molecules of ligand and whether ligand binding results in activation of one or two G-proteins when measured using functional assays in intact living cells. Previously, we demonstrated that serotonin 5-hydroxytryptamine2C (5-HT2C) receptors form homodimers (Herrick-Davis, K., Grinde, E., and Mazurkiewicz, J. (2004) Biochemistry 43, 13963-13971). In the present study, an inactive 5-HT(2C) receptor was created and coexpressed with wild-type 5-HT2C receptors to determine whether dimerization regulates receptor function and to determine the ligand/dimer/G-protein stoichiometry in living cells. Mutagenesis of Ser138 to Arg (S138R) produced a 5-HT2C receptor incapable of binding ligand or stimulating inositol phosphate (IP) signaling. Confocal fluorescence imaging revealed plasma membrane expression of yellow fluorescent protein-tagged S138R receptors. Expression of wild-type 5-HT2C receptors in an S138R-expressing stable cell line had no effect on ligand binding to wild-type 5-HT2C receptors, but inhibited basal and 5-HT-stimulated IP signaling as well as constitutive and 5-HT-stimulated endocytosis of wild-type 5-HT2C receptors. M1 muscarinic receptor activation of IP production was normal in the S138R-expressing cells. Heterodimerization of S138R with wild-type 5-HT2C receptors was visualized in living cells using confocal fluorescence resonance energy transfer (FRET). FRET was dependent on the donor/acceptor ratio and independent of the receptor expression level. Therefore, inactive 5-HT2C receptors inhibit wild-type 5-HT2C receptor function by forming nonfunctional heterodimers expressed on the plasma membrane. These results are consistent with a model in which one GPCR dimer binds two molecules of ligand and one G-protein and indicate that dimerization is essential for 5-HT receptor function.
Fabrication of Superconducting Qubits with Al Trilayer Josephson Junctions (2014)

To implement a large-scale integration of superconducting quantum bits (qubits), we have investigated a process of fabricating submicrometer Al/AlOx/Al trilayer Josephson junctions. Moreover, on the basis of this process, we developed a means of fabricating different kinds of superconducting qubits. Superconducting qubits require not only small junctions, but also peripheral circuit elements, such as a large resonator, on the same chip. As a result, we chose to use planarization in the self-aligned junction contact formation, which suppressed a pattern-area-dependence of the chemical-mechanical polishing rate. In addition, Al fine wires with a width of 0.2 μm were required in some parts of the qubits to increase the coupling strength between the SQUIDs and qubits. We developed a two-step etching process to form such fine wires using i-line photoresist, which had a high etching resistance. The operation of three-junction flux qubits was confirmed in a dilution refrigerator.
Removal of a mirror image and enhancement of the signal-to-noise ratio in Fourier-domain optical coherence tomography using an electro-optic phase modulator (2005)

A novel swept-laser-based Fourier-domain optical coherence tomography system using an electro-optic phase modulator was demonstrated. The imaging range was doubled by cancellation of the mirror image. The elimination of low-frequency noises resulting from dc and autocorrelation terms increased the sensitivity by 20 dB.
A Transparent Conductive Adhesive Laminate Electrode for High‐Efficiency Organic‐Inorganic Lead Halide Perovskite Solar Cells (2014)

A self-adhesive laminate solar-cell electrode is presented based on a metal grid embedded in a polymer film (x-y conduction) and set in contact with the active layer using a pressure-sensitive adhesive containing a very low quantity (1.8%) of organic conductor, which self-organizes to provide z conduction to the grid. This ITO-free material performs in an identical fashion to evaporated gold in high-efficiency perovskite solar cells.
Protease‐resistant peptide design—empowering nature's fragile warriors against HIV (2012)

Peptides have great potential as therapeutic agents, but their use is often limited by susceptibility to proteolysis and their resulting in vivo fragility. In this review, we focus on peptidomimetic approaches to produce protease-resistant peptides with the potential for greatly improved clinical utility. We focus on the use of mirror-image (D-peptide) and ß-peptides as two leading approaches with distinct design principles and challenges. Application to the important and difficult problem of inhibiting HIV entry illustrates the current state-of-the-art in peptidomimetic technologies. We also summarize future directions for this field and highlight remaining obstacles to widespread use of protease-resistant peptides.
Tetanus toxin fragment C fused to flagellin makes a potent mucosal vaccine (2015)

This study establishes FlaB as a successful fusion partner for recombinant subunit tetanus vaccine applicable through mucosal route, and it further endorses our previous observations that FlaB could be a stable adjuvant partner for mucosal vaccines.
Direct Observation of the “Pac-Man” Effect from Dibenzofuran-Bridged Cofacial Bisporphyrins (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDirect Observation of the "Pac-Man" Effect from Dibenzofuran-Bridged Cofacial BisporphyrinsYongqi Deng, Christopher J. Chang, and Daniel G. NoceraView Author Information Department of Chemistry, 6-335 Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge, Massachusetts 02139-4307 Cite this: J. Am. Chem. Soc. 2000, 122, 2, 410–411Publication Date (Web):December 31, 1999Publication History Received16 August 1999Published online31 December 1999Published inissue 1 January 2000https://pubs.acs.org/doi/10.1021/ja992955rhttps://doi.org/10.1021/ja992955rrapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views1913Altmetric-Citations131LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Ligands,Molecular structure,Molecules,Oxygen,Pyrroles Get e-Alerts
Bipyridine:  The Most Widely Used Ligand. A Review of Molecules Comprising at Least Two 2,2‘-Bipyridine Units (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBipyridine: The Most Widely Used Ligand. A Review of Molecules Comprising at Least Two 2,2‘-Bipyridine UnitsChristian Kaes, Alexander Katz, and Mir Wais HosseiniView Author Information Laboratoire de Chimie de Coordination Organique, Institut Le Bel, Université Louis Pasteur, F-67000 Strasbourg, France Cite this: Chem. Rev. 2000, 100, 10, 3553–3590Publication Date (Web):September 14, 2000Publication History Received7 December 1999Published online14 September 2000Published inissue 1 October 2000https://doi.org/10.1021/cr990376zCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views18765Altmetric-Citations960LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (692 KB) Get e-AlertscloseSUBJECTS:Bipyridine,Ligands,Macrocycles,Polymers,Reaction products Get e-Alerts
Design to Cost (1989)

Getting Started. Defining Activities and Responsibilites. Designing for Inherently Low Cost. Choosing Business Strategies. Estimating and Controlling Costs. Remembering History. Appendices. Index.
Aneuploidy in sperm of Hodgkin`s disease patients receiving NOVP chemotherapy (1994)

Induction of genetic damage in germ cells of young patients receiving chemo- or radiotherapy for cancers with probable cure, such as Hodgkin`s disease, is cause for concern. These young patients may someday desire children, and germ cell alterations presenting as numerical chromosomal abnormalities in sperm may place their future offspring at risk. To address this concern, we measured aneuploidy in sperm from eight young Hodgkin`s disease patients: four pre-treatment, four during treatment, and three over a 45 month period following treatment with NOVP (Novantrone, Oncovin, Vinblastine and Prednisone). Patients ranged in stage of disease from IA-IIEB and none had received prior radiation or chemotherapy. Using multi-chromosome sperm FISH with repetitive sequence probes specific for chromosomes X, Y and 8, we found a significant 2-4 fold increase in particular numerical chromosomal abnormalities during treatment which were limited in persistence post-treatment. Additionally, pre-treatment Hodgkin`s disease patients showed elevations in some numerical chromosomal abnormalities when compared to a healthy reference group. In several men, the fraction of aneuploid sperm did not return to healthy reference group levels even after completion of therapy. These results show that elevated sperm aneuploidy occurs in germ cells of young cancer patients during chemotherapy and suggest caution tomore » prevent conceptions during this period. The elevated sperm aneuploidy appears transient, but in some cases never returns to healthy reference group levels.« less