gebhart/patrepeval huggingface dataset:
Natural and Synthetic TLR7 Ligands Inhibit CpG-A- and CpG-C-Oligodeoxynucleotide-Induced IFN-α Production (2007)

Plasmacytoid dendritic cells (pDCs) are unique with respect to their capacity to produce unsurpassed amounts of IFN-alpha and coexpress TLR7 and TLR9, mediating IFN-alpha production. Although TLRs are critical receptors of innate immunity, little is known about the immunological effects of TLR7/TLR9 costimulation. We have analyzed the effects of TLR7/TLR9 costimulation on IFN-alpha production by leukocytes and pDCs. Our experiments revealed that both synthetic (resiquimod and loxoribine) and natural (ssRNA40) TLR7 ligands abrogate CpG-A- and CpG-C-oligodeoxynucleotide (ODN)-induced IFN-alpha production by human leukocytes. Because TLR7 ligands themselves represent important IFN-alpha inducers, we demonstrated that substimulatory TLR7 ligand concentrations significantly inhibited CpG-A-induced IFN-alpha. Delayed addition of TLR7 ligands still resulted in complete suppression of CpG-A-ODN-induced IFN-alpha production, suggesting that the inhibition is unlikely to be caused by a kinetic uptake advantage. Unlike for CpG-A and CpG-C, TLR7 ligands did not inhibit CpG-B-ODN-induced IFN-alpha production. Experiments with purified human pDCs demonstrated that the inhibitory effects of TLR7/TLR9 costimulation were mediated directly by pDCs. Suppression of IFN-alpha production was not related to increased cell death and was also detectable in enriched mouse pDCs. Analyses of pDCs suggested that the TLR7 signal regulates the outcome of TLR7 ligand/CpG-A-ODN costimulation and can either inhibit (IFN-alpha) or promote (IL-8/CD40) cytokine and surface marker expression. Our data reveal for the first time a strong inhibitory effect of TLR7 stimulation on IFN-alpha production induced by CpG-A- and CpG-C-ODNs. These findings provide novel insight into the effects of TLR7/TLR9 costimulation and may support the development of novel TLR9 inhibitors.
HEPARIN‐INDUCED THROMBOCYTOPENIA IN DIALYSIS: The Pathophysiology of Immune‐mediated Heparin‐induced Thrombocytopenia (2003)

Heparin-induced thrombocytopenia (HIT) is an important side effect of heparin therapy associated with significant morbidity and mortality if unrecognized. The platelet count typically falls below 150,000/ micro l 5-14 days after heparin is started. Thrombosis is the major clinical complication. The diagnosis is confirmed with a variety of functional and antigenic assays. Heparin binds to PF4, resulting in a conformational change in the molecule that exposes neo-epitopes that act as immunogens. Antibodies form against the heparin-PF4 complex, the major target antigen. The IgG-heparin-PF4 immune complex binds either via its Fab domain to the platelet surface or via its Fc domain to the FcgammaIIA receptor on the surface of the platelet, resulting in further platelet activation. Continued release of PF4 from activated platelets leads to increasing PF4-heparin complex formation, and a self-propagating cycle of platelet consumption and generation of procoagulant platelet-derived microparticles. Other procoagulant effects of the HIT antibody include endothelial cell damage, stimulation of platelet-leukocyte aggregates, and release of tissue factor from monocytes.
Integrated Nanoreactor Systems:  Triggering the Release and Mixing of Compounds Inside Single Vesicles (2004)

We present a method that allows the on-demand release and mixing of zepto- to femtoliter volumes of solutions in the interior of vesicular nanoreactors. The reactors comprise a nested system of lipid vesicles, part of which release their cargo in the interior of the others during a thermotropic phase transition. The performance of individual reactors immobilized on glass is characterized using confocal microscopy and a fluorescent dye that reports dilution during the release. The results confirm the predicted temperature-induced response and reveal a release transition width of 3 degrees C with a half time of approximately 1 min.
<title>Surface-micromachined mirrors for scalable fiber optic switching applications</title> (2000)

We present design, analysis and characterization of surface- micromachined mirrors developed for fiber-optical cross-connects (OXCs). These mirrors are controlled by electrostatic microactuators, and are optimized for our beam-steering OXC switch architecture. Their geometry leads to high-density switch matrices, and the absence of frictional hinges in their actuation mechanism allows highly repeatable operation. This mirror structure features an adjustable maximum deflection angle that can be set during initial assembly or dynamically varied by integration with a standard surface-micromachined linear actuator. A commercial three-layer polysilicon surface- micromachining process is used for fabrication of the micromirrors.
Multiformat T‐Cell‐Engaging Bispecific Antibodies Targeting Human Breast Cancers (2015)

Four different formats of bispecific antibodies (bsAbs) were generated that consist of anti-Her2 IgG or Fab site-specifically conjugated to anti-CD3 Fab using the genetically encoded noncanonical amino acid. These bsAbs varied in valency or in the presence or absence of an Fc domain. Different valencies did not significantly affect antitumor efficacy, whereas the presence of an Fc domain enhanced cytotoxic activity, but triggered antigen-independent T-cell activation. We show that the bsAbs can efficiently redirect T cells to kill all Her2 expressing cancer cells, including Her2 1+ cancers, both in vitro and in rodent xenograft models. This work increases our understanding of the structural features that affect bsAb activity, and underscores the potential of bsAbs as a promising therapeutic option for breast cancer patients with low or heterogeneous Her2 expression.
freeIbis: an efficient basecaller with calibrated quality scores for Illumina sequencers (2013)

FreeIbis is freely available for use under the GPL (http://bioinf.eva.mpg.de/freeibis/). It requires a Python interpreter and a C++ compiler. Tailored versions of LIBOCAS and LIBLINEAR are distributed along with the package.
Elongation factor SII-dependent transcription by RNA polymerase II through a sequence-specific DNA-binding protein. (1993)

In eukaryotes the genetic material is contained within a coiled, protein-coated structure known as chromatin. RNA polymerases must recognize specific nucleoprotein assemblies and maintain contact with the underlying DNA duplex for many thousands of base pairs. Template-bound lac operon repressor from Escherichia coli arrests RNA polymerase II in vitro and in vivo [Kuhn, A., Bartsch, I. & Grummt, I. (1990) Nature (London) 344, 559-562; Deuschele, U., Hipskind, R. A. & Bujard, H. (1990) Science 248, 480-483]. We show that in a reconstituted transcription system, elongation factor SII enables RNA polymerase II to proceed through this blockage at high efficiency. lac repressor-arrested elongation complexes display an SII-activated transcript cleavage reaction, an activity associated with transcriptional read-through of a previously characterized region of bent DNA. This demonstrates factor-dependent transcription by RNA polymerase II through a sequence-specific DNA-binding protein. Nascent transcript cleavage may be a general mechanism by which RNA polymerase II can bypass many transcriptional impediments.
N-Fluoroalkylated and N-alkylated analogs of the dopaminergic D-2 receptor antagonist raclopride (1990)

A series of raclopride [(S)-2-[(3,5-dichloro-6-methoxy-2- hydroxybenzamido)methyl]-1-ethylpyrrolidine] derivatives bearing pyrrolidino N-fluoroalkyl or -alkyl substituents were synthesized and evaluated as potential dopaminergic receptor-based positron tomography radiopharmaceuticals. Radiosynthetic procedures for producing the corresponding N-[18F]fluoroalkylated analogues of raclopride from 18F- (beta+, t1/2 = 110 min) in high specific activity were also developed. In vitro binding assays using competitive displacement of [3H]spiperone from primate caudate tissue indicated that the N-alkylated analogues of raclopride had Ki values of 5-40 nM, whereas the corresponding values for analogous N-fluoroalkylated derivatives ranged from 90-160 nM. The relatively low D-2 binding affinity of these fluorinated salicylamides was corroborated by in vivo tissue biodistribution results in rodents. On the basis of structure-binding correlations, the impact of intramolecular hydrogen bonding, ligand basicity, and steric bulk on the affinity of the benzamides for D-2 receptor binding are discussed. Strategies are presented for the development of alternative fluorinated salicylamides that are both receptor active and metabolically stable.
Efficacy of Flibanserin in Women with Hypoactive Sexual Desire Disorder: Results from the BEGONIA Trial (2013)

In premenopausal women with HSDD, flibanserin 100 mg qhs resulted in significant improvements in the number of SSE and sexual desire (FSFI desire domain score) vs. placebo. Flibanserin was associated with significant reductions in distress associated with sexual dysfunction (FSDS-R total score) and distress associated with low sexual desire (FSDS-R Item 13) vs. placebo. There were no significant safety concerns associated with the use of flibanserin for 24 weeks.
Physiology of hot flashes (2001)

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.
Reactivity of Nitroxyl-Derived Sulfinamides (2012)

Sulfinamide [RS(O)NH(2)] formation is known to occur upon exposure of cysteine residues to nitroxyl (HNO), which has received recent attention as a potential heart failure therapeutic. Because this modification can alter protein structure and function, we have examined the reactivity of sulfinamides in several systems, including a small organic molecule, peptides, and a protein. Although it has generally been assumed that this thiol to sulfinamide modification is irreversible, we show that sulfinamides can be reduced back to the free thiol in the presence of excess thiol at physiological pH and temperature. We have examined this sulfinamide reduction both in peptides, where a cyclic intermediate analogous to that proposed for asparagine deamidation reactions potentially can contribute, and in a small organic molecule, where the mechanism is restricted to a direct thiolysis. These studies suggest that the contribution from the cyclic intermediate becomes more important in environments with lower dielectric constants. In addition, although sulfinic acid [RS(O)OH] formation is observed upon prolonged incubations in water, reduction of sulfinamides is found to dominate in the presence of thiols. Finally, studies with the cysteine protease, papain, suggest that the reduction of sulfinamide to the free thiol is viable in a protein environment.
Identification of a BALB/c H-2L d Gene by DNA-Mediated Gene Transfer (1982)

Gene transfer and immunoselection were used in the identification of a BALB/c genomic clone containing an H-2Ld gene (clone 27.5). Transformation of thymidine kinase-negative C3H mouse L cells with the cloned 27.5 DNA together with the herpes simplex virus tk gene produced transformants expressing Ld molecules detected by radioimmune assay with monoclonal hybridoma antibodies to Ld antigens. The foreign Ld gene products expressed by cloned mouse L cell transformants were shown to be virtually indistinguishable from BALB/c spleen Ld molecules by two-dimensional electrophoretic analysis of H-2Ld immunoprecipitates. These results indicate that the genomic clone 27.5 contains a functional BALB/c H-2Ld gene and demonstrate the usefulness of this approach for identifying the gene products encoded by cloned genes which are members of a multigene family. Furthermore, the ability to place cell-surface recognition molecules on the surfaces of foreign cells provides a powerful opportunity for functional analyses of these molecules.
Visualisation of the Semantic Web: Topic Maps visualisation (2003)

Topic Maps provide a bridge between the domains of knowledge representation and information management by building a structured semantic network above information resources. Our research at LIP6 aims at visualizing this semantic layer efficiently, which is a critical issue as Topic Maps may contain millions of elements. This paper is divided into two parts. First, we depict briefly basic Topic Maps concepts. Then, we discuss Topic Maps visualisation requirements and we study how existing visualisation techniques may be applied to Topic Maps representation. We conclude by giving a few directions that could lead to the "ultimate" Topic Map visualisation tool.
Coordinate Regulation of β-Lactamase Induction and Peptidoglycan Composition by the Amp Operon (1991)

The amp operon, which is located on the Escherichia coli chromosome, modulates the induction of plasmid-borne beta-lactamase genes by extracellular beta-lactam antibiotics. This suggests that the gene products AmpD and AmpE may function in the transduction of external signals. beta-Lactam antibiotics are analogs of cell wall components that can be released during cell wall morphogenesis of enterobacteria. The amp operon was studied to determine its importance in signal transduction during cell wall morphogenesis. The peptidoglycan compositions of amp mutants were determined by high-performance liquid chromatography and fast atom bombardment mass spectrometry. When a chromosomal or plasmid-borne copy of ampD was present, the amount of pentapeptide-containing muropeptides in the cell wall increased upon addition of the cell wall constituent diaminopimelic acid to the growth medium. These results suggest that beta-lactamase induction and modulation of the composition of the cell wall share elements of a regulatory circuit that involves AmpD. Escherichia coli requires AmpD to respond to extracellular signaling amino acids, such as diaminopimelic acid, and this signal transduction system may regulate peptidoglycan composition in response to cell wall turnover products.
Osteopontin stimulates gelsolin-associated phosphoinositide levels and phosphatidylinositol triphosphate-hydroxyl kinase. (1996)

Based on previous studies demonstrating activation of phosphatidylinositol 3-hydroxyl kinase (PI3-kinase) and stimulation of a change in cell shape, we examined the effect of osteopontin on the association of phospholipids with gelsolin, an actin-capping/severing protein. Osteopontin stimulated a rapid increase in phosphatidylinositol bisphosphate and phosphatidylinositol triphosphate levels associated with gelsolin in Triton-soluble fractions of cell lysates. The increased levels of phosphatidylinositol triphosphate associated with gelsolin were due to stimulation of PI3-kinase activity associated with gelsolin in the Triton-soluble fractions, and they were blocked by the PI3-kinase inhibitor wortmannin. Osteopontin stimulated translocation of PI3-kinase from the Triton-insoluble to Triton-soluble gelsolin. Osteopontin also decreased Triton-soluble gelsolin/actin complexes consistent with actin uncapping, and increased F-actin levels, which were also blocked by wortmannin. The osteopontin effects were mediated through binding to the alpha(v)beta 3 integrin. Taken together, our studies indicate that osteopontin/alpha(v)beta 3-mediated changes in gelsolin-associated phosphoinositide levels and PI3-kinase activity are related to stimulation of F-actin formation in osteoclasts.
Close Monitoring of Gel Based Conformance Control by NMR Techniques (2017)

Abstract Carbonate's extreme heterogeneity in the form of fracture corridors and super-permeability thief zones challenges the efficient sweep of oil in both secondary and tertiary recovery operations. In such reservoirs, conformance control is crucial to ensure injected water and any EOR chemicals optimally contact the remaining oil with minimal throughput. Gel-based conformance control has been successfully applied on both sandstone and carbonate reservoirs. However, in-depth conformance control in high temperature reservoirs is still a challenge, due to severe gel syneresis (expulsion of a liquid from a gel) and the associated significant reduction in gelation time. Recently, we have demonstrated the potential of a selected gel formulation and its favorable impact on sweep efficiency for both water and chemical flooding applications in high temperature and high salinity carbonates (Wang, 2016). In the current work, the performance of polyacrylamide/chromium gel injection followed by water flooding for Arab-D carbonate reservoir rock was closely monitored by 1D T2, spatial NMR T2 mapping and 2D NMR techniques. The NMR measurements before and after waterflooding with and without pre-injection of gel provided the detailed description of spatial oil recovery along the rock core sample under reservoir condition. By comparing the spatial T2 distributions from the experiment with waterflooding and gel injection followed by waterflooding for the core sample with artificial wormhole drilled in the center, which mimics the fluid thief zone, the efficiency of the conformance control by gel was measured. The incremental oil recovery factor of ~14% OOIC after gel injection followed by waterflooding was observed throughout the whole sample with highest recovery in the vicinity of where the wormhole begins near fluid injection inlet. In addition, by analyzing the alteration of spatial NMR T2 and T2-D distribution, the accurate flow paths of the injected water and gel were derived from NMR data. The results of the current study increase the understanding of how gel could helps to increase sweep efficiency of waterflooding and other IOR/EOR applications in the presence of unwanted highly permeable channels in the reservoir rocks.
Establishment of human endothelial cell lines in a serum-free culture and its application for expression of transfected prepro endothelin gene. (1991)

Endothelial cells cover the inner layer of vascular tube and are involved in the pathogenesis of some diseases in heart and brain. A development of endothelial cell lines in a serum-free culture lead to our discovery of endothelin (ET) and is expected to be breakthrough for other new fields of medical science. In this paper, we report establishment of vascular endothelial cell lines in serum-free and protein-free culture, transfection of prepro ET cDNA into them, and it's expression and processing to mature ET. A human endothelial cell line, ECV304, has been subcultivated in medium with 10% fetal bovine serum. We tested serum-free culture of this cell line and a several months later, established a cell line, t-HUE2 which would show stable growth in serum-free medium ASF301 containing EGF, insulin, transferrin and albumin as protein components. After additional 12-months' struggle for obtaining a new cell line which can grow without any protein components, we established t-HUE4 cell line which can be subcultivated in basal medium of HamF-12. Although the cell line was derived from human umbilical vein endothelial cells, production and secretion of ET by the cell line into culture medium was not detected with radioimmunoassay method. By transfecting prepro ET cDNA into t-HUE2 and Raji (a human B cell line), we examined the regulation of gene expression in the transformed t-HUE2 and Raji cell lines. The results indicated that all the transformants expressed high level of prepro ET mRNA but that Raji transformant did not produce detectable amounts of ET nor ER precursor protein (big ET). In addition, conversion ratio of ET to big ET in t-HUE2 transformants was much higher than those in normal endothelial cells. Thus, post-transcriptional regulation of prepro ET gene in human B lymphocyte cell line and induction of ET converting enzyme in human vascular endothelial cell line were suggested. In addition to the present study, usefulness of t-HUE2 cell line in serum-free culture for the production of human-type glycoproteins was discussed.
Challenges and prospects of 3D micro-supercapacitors for powering the internet of things (2018)

The fabrication of miniaturized electrochemical energy storage systems is essential for the development of future electronic devices for Internet of Thing applications. This paper aims at reviewing the current micro-supercapacitor technologies and at defining the guidelines to produce high performance micro-devices with special focuses onto the 3D designs as well as the fabrication of solid state miniaturized devices to solve the packaging issue.
Rapid Kinetics of Na+ Binding to Thrombin (2006)

The kinetic mechanism of Na(+) binding to thrombin was resolved by stopped-flow measurements of intrinsic fluorescence. Na(+) binds to thrombin in a two-step mechanism with a rapid phase occurring within the dead time of the spectrometer (<0.5 ms) followed by a single-exponential slow phase whose k(obs) decreases hyperbolically with increasing [Na(+)]. The rapid phase is due to Na(+) binding to the enzyme E to generate the E:Na(+) form. The slow phase is due to the interconversion between E(*) and E, where E(*) is a form that cannot bind Na(+). Temperature studies in the range from 5 to 35 degrees C show significant enthalpy, entropy, and heat capacity changes associated with both Na(+) binding and the E to E(*) transition. As a result, under conditions of physiologic temperature and salt concentrations, the E(*) form is negligibly populated (<1%) and thrombin is almost equally partitioned between the E (40%) and E:Na(+) (60%) forms. Single-site Phe mutations of all nine Trp residues of thrombin enabled assignment of the fluorescence changes induced by Na(+) binding mainly to Trp-141 and Trp-215, and to a lesser extent to Trp-148, Trp-207, and Trp-237. However, the fast phase of fluorescence increase is influenced to different extents by all Trp residues. The distribution of these residues over the entire thrombin surface demonstrates that Na(+) binding induces long-range effects on the structure of the enzyme as a whole, contrary to the conclusions drawn from recent structural studies. These findings elucidate the mechanism of Na(+) binding to thrombin and are relevant to other clotting factors and enzymes allosterically activated by monovalent cations.