gebhart/patrepeval huggingface dataset:
Cyclolinopeptides and their analogs--a new family of peptide immunosuppressants affecting the calcineurin system. (1999)

The results of the investigation of immunosuppressive activity of cyclolinopeptide A (CLA--cyclic hydrophobic nonapeptide present in the linseeds) and its analogs are discussed. The results obtained for other natural cyclic peptides showing structural similarities with CLA (antamanide, cycloamanides, hymenistatin, hymenamides) are also reviewed. It results from these investigations that the molecular mechanism of the CLA action is the same as that of cyclosporin A and FK-506 compound, i.e. it consists in formation of the complex with cyclophilin and inhibition--in this form--of the phosphatase activity of calcineurin. The results also suggest that the immunosuppressive activity of these compounds resides in their--Pro-Xxx-Phe- fragment, where Xxx is a hydrophobic (e.g. Leu, Val) or aromatic amino acid residue.
Neurotoxins of Animal Venoms: Snakes (1973)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient (2018)

Sensory function significantly improved in this man following VNS paired with tactile stimulation. This approach merits further study in controlled clinical trials.
Fabrication of a double-side IGBT by very low temperature wafer bonding (2003)

A bidirectional double-side IGBT has been successfully fabricated by very low temperature direct wafer bonding for the first time. The utility of the second MOS gate to control hole injection is demonstrated. Through optimized switching of the second gate, a 50% decrease in switching loss is observed.
A Digitally Modulated Polar CMOS PA with 20MHz Signal BW (2007)

A polar PA employs an array of 64 constant-envelope amplifiers that are activated digitally using 4times oversampling and interpolation to support 64QAM OFDM signals. Implemented in 0.18 μm CMOS, the amplifier operates at 1.6GHz with 20MHz signal BW and achieves 7.2% PAE with -26.8dB EVM while delivering 13.6dBm linear output power.
Histone deacetylase. Association with a nuclease resistant, high molecular weight fraction of HeLa cell chromatin. (1983)

The chromatin-bound histone deacetylase of HeLa cells has been studied using endogenous [3H]acetyl-labeled polynucleosomes containing the enzyme, prepared in the presence of 40 mM butyrate. Histone deacetylase was assayed upon removal of the butyrate, and it was found that active enzyme is found only in association with a high molecular weight complex. This deacetylase-containing complex is relatively resistant to digestion with micrococcal nuclease. No activity is found on mononucleosomes or oligonucleosomes. Up to 90% of labeled acetyl groups are removed from histone deacetylase complexes incubated in the absence of butyrate. Free histones are a poor substrate under these conditions, but histones in mononucleosomes are deacetylated when they are incubated with histone deacetylase complex. Histone deacetylase remains bound to this complex in 1-2 M NaCl and does not dissociate from it during its reaction with acetylated core histones. Under typical nuclease digestion conditions, the histone deacetylase complex contains DNA with a size distribution of 5-11 kilobase pairs and a variety of nonhistone proteins. Comparison of the protein composition of histone deacetylase complexes with that of nuclear matrix preparations shows some similarities. Taken together, the results on the chromatographic behavior, the DNA fragment sizes, and the protein composition of the deacetylase complex suggest that protein-protein interactions may be important in maintaining its structure and also in the binding of the deacetylase itself to the complex.
Antimicrobial and Chemoattractant Activity, Lipopolysaccharide Neutralization, Cytotoxicity, and Inhibition by Serum of Analogs of Human Cathelicidin LL-37 (2005)

Antimicrobial peptides have been evaluated in vitro and in vivo as alternatives to conventional antibiotics. Apart from being antimicrobial, the native human cathelicidin-derived peptide LL-37 (amino acids [aa] 104 to 140 of the human cathelicidin antimicrobial peptide) also binds and neutralizes bacterial lipopolysaccharide (LPS) and might therefore have beneficial effects in the treatment of septic shock. However, clinical trials have been hampered by indications of toxic effects of LL-37 on mammalian cells and evidence that its antimicrobial effects are inhibited by serum. For the present study, LL-37 was compared to two less hydrophobic fragments obtained by N-terminal truncation, named 106 (aa 106 to 140) and 110 (aa 110 to 140), and to a previously described more hydrophobic variant, the 18-mer LLKKK, concerning antimicrobial properties, lipopolysaccharide neutralization, toxicity against human erythrocytes and cultured vascular smooth muscle cells, chemotactic activity, and inhibition by serum. LL-37, fragments 106 and 110, and the 18-mer LLKKK inhibited the growth of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans in a radial diffusion assay, inhibited lipopolysaccharide-induced vascular nitric oxide production, and attracted neutrophil granulocytes similarly. While fragments 106 and 110 caused less hemolysis and DNA fragmentation in cultured cells than did LL-37, the 18-mer LLKKK induced severe hemolysis. The antibacterial effect of fragments 106 and 110 was not affected by serum, while the effect of LL-37 was reduced. We concluded that the removal of N-terminal hydrophobic amino acids from LL-37 decreases its cytotoxicity as well as its inhibition by serum without negatively affecting its antimicrobial or LPS-neutralizing action. Such LL-37-derived peptides may thus be beneficial for the treatment of patients with sepsis.
Nerve growth factor governs the enhanced ability of opioids to suppress inflammatory pain (2006)

Nerve growth factor (NGF) regulates sensory neuron phenotype by elevated expression of ion channels and receptors contributing to pain. Peripheral opioid antinociception is dependent on sensory neuron mu opioid receptor (MOR) expression, coupling and efficacy. This study investigates the role of NGF in the upregulation of the number and efficacy of sensory MORs rendering sites of painful inflammation more susceptible to opioids. We identified co-localization of MOR with calcitonin gene-related peptides (CGRP) and with the NGF receptors tyrosine receptor kinase (TrkA) and p75(NTR) within rat dorsal root ganglia (DRG). We showed that unilateral hind paw inflammation induced with Freund's complete adjuvant (FCA) or intraplantar (i.pl.) NGF increased NGF's retrograde transport and MOR expression in TrkA positive DRG which was prevented by the disruption of this NGF transport. MOR upregulation in DRG was followed by enhanced axonal MOR transport towards peripheral nerve terminals and subsequent increase of MOR-ir nerve fibres within skin. Furthermore, peripheral antinociception elicited by i.pl. fentanyl was naloxone reversible and potentiated exclusively in inflamed and NGF-treated paws. Both FCA- and NGF-induced effects occurring through DRG to peripheral nerve fibres and the potentiation of antinociception were abrogated by NGF neutralization. Therefore, our results suggest that NGF not only contributes to inflammatory pain but also governs the upregulation in the number and efficacy of sensory neuron MOR, resulting in enhanced opioid susceptibility towards better pain control. This suggests the potential to overcome the unresponsiveness to opioids of certain neuropathic pain states.
Lymphotoxin-β receptor signaling complex: Role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor κB (1997)

The binding of heterotrimeric lymphotoxin, LT alpha1 beta2, to the LTbeta receptor (LTbeta R), a member of the tumor necrosis factor receptor (TNFR) superfamily, induces nuclear factor kappaB (NF-kappaB) activation and cell death in HT29 adenocarcinoma cells. We now show that treatment with LT alpha1 beta2 or agonistic LTbeta R antibodies causes rapid recruitment of TNFR-associated factor 3 (TRAF3) to the LTbeta R cytoplasmic domain. Further, stable overexpression of a TRAF3 mutant that lacks the RING and zinc finger domains inhibits LTbeta R-mediated cell death. The inhibition is specific for LTbeta R cell death signaling, since NF-kappaB activation by LT alpha1 beta2 and Fas-mediated apoptosis are not inhibited in the same cells. The mutant and endogenous TRAF3s are both recruited at equimolar amounts to the LTbeta R, suggesting that the mutant disrupts the function of the signaling complex. These results implicate TRAF3 as a critical component of the LTbeta R death signaling complex and indicate that at least two independent signaling pathways are initiated by LTbeta R ligation.
Engineered Recognition of Tetravalent Zirconium and Thorium by Chelator–Protein Systems: Toward Flexible Radiotherapy and Imaging Platforms (2016)

Targeted α therapy holds tremendous potential as a cancer treatment: it offers the possibility of delivering a highly cytotoxic dose to targeted cells while minimizing damage to surrounding healthy tissue. The metallic α-generating radioisotopes <sup>225</sup>Ac and <sup>227</sup>Th are promising radionuclides for therapeutic use, provided adequate chelation and targeting. Here we demonstrate a new chelating platform composed of a multidentate high-affinity oxygen-donating ligand 3,4,3-LI(CAM) bound to the mammalian protein siderocalin. Respective stability constants log β<sub>110</sub> = 29.65 ± 0.65, 57.26 ± 0.20, and 47.71 ± 0.08, determined for the Eu<sup>III</sup> (a lanthanide surrogate for Ac<sup>III</sup>), Zr<sup>IV</sup>, and Th<sup>IV</sup> complexes of 3,4,3-LI(CAM) through spectrophotometric titrations, reveal this ligand to be one of the most powerful chelators for both trivalent and tetravalent metal ions at physiological pH. The resulting metal-ligand complexes are also recognized with extremely high affinity by the siderophore-binding protein siderocalin, with dissociation constants below 40 nM and tight electrostatic interactions, as evidenced by X-ray structures of the protein:ligand:metal adducts with Zr<sup>IV</sup> and Th<sup>IV</sup>. Finally, differences in biodistribution profiles between free and siderocalin-bound <sup>238</sup>Pu<sup>IV</sup>-3,4,3-LI(CAM) complexes confirm in vivo stability of the protein construct. The siderocalin:3,4,3-LI(CAM) assembly can therefore serve as a "lock" to consolidate binding to the therapeutic <sup>225</sup>Ac and <sup>227</sup>Th isotopes or to the positron emission tomography emitter <sup>89</sup>Zr, independent of metal valence state.
Genetic modification of cassava for enhanced starch production (2006)

To date, transgenic approaches to biofortify subsistence crops have been rather limited. This is particularly true for the starchy root crop cassava (Manihot esculenta Crantz). Cassava has one of the highest rates of CO(2) fixation and sucrose synthesis for any C3 plant, but rarely reaches its yield potentials in the field. It was our hypothesis that starch production in cassava tuberous roots could be increased substantially by increasing the sink strength for carbohydrate. To test this hypothesis, we generated transgenic plants with enhanced tuberous root ADP-glucose pyrophosphorylase (AGPase) activity. This was achieved by expressing a modified form of the bacterial glgC gene under the control of a Class I patatin promoter. AGPase catalyses the rate-limiting step in starch biosynthesis, and therefore the expression of a more active bacterial form of the enzyme was expected to lead to increased starch production. To facilitate maximal AGPase activity, we modified the Escherichia coli glgC gene (encoding AGPase) by site-directed mutagenesis (G336D) to reduce allosteric feedback regulation by fructose-1,6-bisphosphate. Transgenic plants (three) expressing the glgC gene had up to 70% higher AGPase activity than control plants when assayed under conditions optimal for plant and not bacterial AGPase activity. Plants having the highest AGPase activities had up to a 2.6-fold increase in total tuberous root biomass when grown under glasshouse conditions. In addition, plants with the highest tuberous root AGPase activity had significant increases in above-ground biomass, consistent with a possible reduction in feedback inhibition on photosynthetic carbon fixation. These results demonstrate that targeted modification of enzymes regulating source-sink relationships in crop plants having high carbohydrate source strengths is an effective strategy for increasing carbohydrate yields in sink tissues.
Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study (2011)

Elevated concentrations of the oxidative stress marker MPO were independently associated with increased risk of incident CHD. This finding deserves detailed evaluation in further studies.
Expanding the Genetic Alphabet:  Non-Epimerizing Nucleoside with the pyDDA Hydrogen-Bonding Pattern (2003)

6-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)-5-nitro-1H-pyridin-2-one (4), a C-glycoside exhibiting the nonstandard pyDDA hydrogen-bonding pattern, was synthesized via Heck coupling. The nitro group greatly enhances the stability of the nucleoside toward acid-catalyzed epimerization without leading to significant deprotonation of the heterocycle at physiological pH. These results make nucleoside 4 a promising candidate for an expanded genetic alphabet.
Multi‐Chromatic pH‐Activatable 19F‐MRI Nanoprobes with Binary ON/OFF pH Transitions and Chemical‐Shift Barcodes (2013)

Imaging all the people: Using ionizable diblock copolymers a series of nanoprobes encoded with different 19F reporters for specific pH transitions is prepared for use in MRI. The pH response of the nanoprobes is extremely sharp (ΔpHON/OFF≈0.25 pH), and results from the disassembly of polymer micelles (see scheme). A collection of three nanoprobes provides the proof of concept and allows for a qualitative measurement of environmental pH values. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells. (1996)

The functional receptor complexes assembled in response to interleukin-6 and -11 (IL-6 and IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF), all involve the signal transducer gp130: IL-6 and IL-11 induce homodimerization of gp130, while the rest heterodimerize gp130 with other gp130-related beta subunits. Some of these cytokines (IL-6, IL-11, and CNTF) also require a specificity-determining alpha subunit not directly involved in signaling. We have searched for functional receptor complexes for these cytokines in cells of the bone marrow stromal/osteoblastic lineage, using tyrosine phosphorylation of the beta subunits as a detection assay. Collectively, murine calvaria cells, bone marrow-derived murine cell lines (+/+LDA11 and MBA13.2), as well as murine (MC3T3-E1) and human (MG-63) osteoblast-like cell lines displayed all the previously recognized alpha and beta subunits of this family of receptors. However, individual cell types had different constellations of alpha and beta subunits. In addition and in difference to the other cell types examined, MC3T3-E1 cells expressed a heretofore unrecognized form of gp130; and MG-63 displayed an alternative form (type II) of the OSM receptor. These findings establish that stromal/osteoblastic cells are targets for the actions of all the members of the cytokine subfamily that shares the gp130 signal transducer; and suggest that different receptor repertoires may be expressed at different stages of differentiation of this lineage.
Correction of phase distortion in spatial heterodyne spectroscopy (2004)

The detailed analysis of measured interferograms generally requires phase correction. Phase-shift correction methods are commonly used and well documented for conventional Fourier-transform spectroscopy. However, measured interferograms can show additional phase errors, depending on the optical path difference and signal frequency, which we call phase distortion. In spatial heterodyne spectroscopy they can be caused, for instance, by optical defects or image distortions, making them a characteristic of the individual spectrometer. They can generally be corrected without significant loss of the signal-to-noise ratio. We present a technique to measure phase distortion by using a measured example interferogram. We also describe a technique to correct for phase distortion and test its performance by using a simulation with a near-UV solar spectrum. We find that for our measured example interferogram the phase distortion is small and nearly frequency independent. Furthermore, we show that the presented phase-correction technique is especially effective for apodized interferograms.
Periosteal Cells in Bone Tissue Engineering (2003)

In 1742, H.L. Duhamel published a report in which the osteogenic function of periosteum was described. In 1932 H.B. Fell was the first to successfully culture periosteum; Fell concluded that this tissue might have the capability to form mineralized tissue in vitro. In the 1990s the research group of A.L. Caplan pioneered work exploring the osteogenic potential of periosteal cells in the field of bone engineering. On the basis of these studies a number of research groups have developed hard tissue generation concepts that aim to repeat the clinical success of bone autografts by culturing cells from periosteum and seeding a sufficient quantity of those cells into scaffolds made of biomaterials of natural and synthetic origin. The highly porous matrices support the induction of bone regeneration by creating and maintaining a space that facilitates progenitor cell migration, proliferation, and differentiation as well as graft revascularization. In this way, a host tissue-scaffold cell interphase might be created that allows reproduction of the intrinsic properties of autogenous bone, including the ability to be incorporated into the surrounding host bone and to continue normal bone-remodeling processes. This review discusses the history and state of the art of bone tissue engineering from a periosteum and periosteal cell source point of view and attempts to indicate future research directions.
Towards generic adiabatic elimination for bipartite open quantum systems (2017)

We consider a composite open quantum system consisting of a fast subsystem coupled to a slow one. Using the time-scale separation, we develop an adiabatic elimination technique to derive at any order the reduced model describing the slow subsystem. The method, based on an asymptotic expansion and geometric singular perturbation theory, ensures the physical interpretation of the reduced second-order model by giving the reduced dynamics in a Lindblad form and the state reduction in Kraus map form. We give explicit second-order formulas for Hamiltonian or cascade coupling between the two subsystems. These formulas can be used to engineer, via a careful choice of the fast subsystem, the Hamiltonian and Lindbald operators governing the dissipative dynamics of the slow subsystem.
Sphingosine‐1‐Phosphate as an Intercellular Signaling Moleculea (1998)

Sphingosine-1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. Previously, we found the roles of Sph-1-P as a platelet activating lipid released from stimulated platelets and as a lipid regulator of cell motility. We first investigated the mechanism by which Sph-1-P induces activation in platelets. Although exogenous Sph-1-P activated platelets, intracellular Sph-1-P formed from exogenously added Sph failed to do so. Supporting the notion that exogenous Sph-1-P stimulates platelets from outside, we found that contact of platelet surfaces with Sph-1-P-immobilized glass beads resulted in platelet activation. Using these glass beads, we next found that exogenously added Sph-1-P inhibits F10 cell motility from outside through its specific binding site(s) on the cell. We finally identified putative receptor protein(s) for Sph-1-P on the surface of F10 cells.
Electrophysiologic and morphologic effects of ophthalmic preparations on rabbit cornea epithelium. (1977)

The effects of several components of ophthalmic preparations on isolated rabbit cornea were studied by continuous electrophysiologic monitoring followed by fixation for scanning electron microscopy (SEM). Benzalkonium chloride (0.001 percent), thimerosal (0.0004 percent), and amphotericin B (0.0025 percent) all briefly increased ion transport, then greatly decreased epithelial resistance. Severe disruption of surface cell layers occurred simultaneously with resistance decrease. Silver nitrate (0.00017 percent) stimulated transport with less accompanying morphologic damage. Tetracaine (0.05 percent) disrupted epithelial function and caused exfoliation of several cell layers. Chlorobutanol (0.1 percent) produced a nearly complete loss of the squamous cell layer. Chloramphenicol, epinephrine, and pilocarpine produced minor changes in structure and electrophysiology at full clinical concentration. It was concluded that low concentrations of preservatives in ophthalmic preparations disrupt the barrier and transport properties of the corneal epithelium.