gebhart/patrepeval huggingface dataset:
Caenorhabditis elegans Gαq Regulates Egg-Laying Behavior via a PLCβ-Independent and Serotonin-Dependent Signaling Pathway and Likely Functions Both in the Nervous System and in Muscle (2003)

egl-30 encodes the single C. elegans ortholog of vertebrate Galphaq family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the nervous system and in pharyngeal muscle. We isolated dominant, gain-of-function alleles of egl-30 as intragenic revertants of an egl-30 reduction-of-function mutation. Using these gain-of-function mutants and existing reduction-of-function mutants, we examined the site and mode of action of EGL-30. On the basis of pharmacological analysis, it has been determined that egl-30 functions both in the nervous system and in the vulval muscles for egg-laying behavior. Genetic epistasis over mutations that eliminate detectable levels of serotonin reveals that egl-30 requires serotonin to regulate egg laying. Furthermore, pharmacological response assays strongly suggest that EGL-30 may directly couple to a serotonin receptor to mediate egg laying. We also examined genetic interactions with mutations in the gene that encodes the single C. elegans homolog of PLCbeta and mutations in genes that encode signaling molecules downstream of PLCbeta. We conclude that PLCbeta functions in parallel with egl-30 with respect to egg laying or is not the major effector of EGL-30. In contrast, PLCbeta-mediated signaling is likely downstream of EGL-30 with respect to pharyngeal-pumping behavior. Our data indicate that there are multiple signaling pathways downstream of EGL-30 and that different pathways could predominate with respect to the regulation of different behaviors.
LDP Extensions for Hub and Spoke Multipoint Label Switched Path (2014)

This document introduces a hub and spoke multipoint (HSMP) Label
Switched Path (LSP), which allows traffic from root to leaf through
point-to-multipoint (P2MP) LSPs and also leaf to root along the
reverse path. That means traffic entering the HSMP LSP from the
application/customer at the root node travels downstream to each leaf
node, exactly as if it were traveling downstream along a P2MP LSP to
each leaf node. Upstream traffic entering the HSMP LSP at any leaf
node travels upstream along the tree to the root, as if it were
unicast to the root. Direct communication among the leaf nodes is not
allowed.
Improving the Outcome of Leukemia by Natural Killer Cell-Based Immunotherapeutic Strategies (2014)

Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells are widely recognized as potent anti-leukemia mediators. Alloreactive donor NK cells have been shown to improve the outcome of allogeneic stem-cell transplantation for leukemia. In addition, in vivo transfer of NK cells may soon reveal an important therapeutic tool for leukemia, if tolerance to NK-mediated anti-leukemia effects is overcome. This will require, at a minimum, the ex vivo generation of a clinically safe NK cell product containing adequate numbers of NK cells with robust anti-leukemia potential. Ideally, ex vivo generated NK cells should also have similar anti-leukemia potential in different patients, and be easy to obtain for convenient clinical scale-up. Moreover, optimal clinical protocols for NK therapy in leukemia and other cancers are still lacking. These and other issues are being currently addressed by multiple research groups. This review will first describe current laboratory NK cell expansion and differentiation techniques by separately addressing different NK cell sources. Subsequently, it will address the mechanisms known to be responsible for NK cell alloreactivity, as well as their clinical impact in the hematopoietic stem cells transplantation setting. Finally, it will briefly provide insight on past NK-based clinical trials.
Hindered Molecular Reorientation of Lithium Ion Doped Succinonitrile in the Terahertz Range (2014)

The THz range permittivity of succinonitrile exhibits Debye like behavior in its plastic crystal phase, with a characteristic Cole Cole relaxation time of 65ps ±17ps which increases considerably in the presence of ionic dopants.
Lift Optimization Study of a Multi-Element Three-Segment Variable Camber Airfoil (2016)

This paper reports a detailed computational high-lift study of the Variable Camber Continuous Trailing Edge Flap (VCCTEF) system carried out to explore the best VCCTEF designs, in conjunction with a leading edge flap called the Variable Camber Krueger (VCK), for take-off and landing. For this purpose, a three-segment variable camber airfoil employed as a performance adaptive aeroelastic wing shaping control effector for a NASA Generic Transport Model (GTM) in landing and take-off configurations is considered. The objective of the study is to define optimal high-lift VCCTEF settings and VCK settings/configurations. A total of 224 combinations of VCK settings/configurations and VCCTEF settings are considered for the inboard GTM wing, where the VCCTEFs are configured as a Fowler flap that forms a slot between the VCCTEF and the main wing. For the VCK settings of deflection angles of 55deg, 60deg and 65deg, 18, 19 and 19 vck configurations, respectively, were considered for each of the 4 different VCCTEF deflection settings. Different vck configurations were defined by varying the horizontal and vertical distance of the vck from the main wing. A computational investigation using a Reynolds-Averaged Navier-Stokes (RANS) solver was carried out to complement a wind-tunnel experimental study covering three of these configurations with the goal of identifying the most optimal high-lift configurations. Four most optimal high-lift configurations, corresponding to each of the VCK deflection settings, have been identified out of all the different configurations considered in this study yielding the highest lift performance.
Transient Birefringence of Elastomeric Polypropylene Subjected to Step Shear Strain (1999)

The step shear strain behavior of elastomeric polypropylene (ePP) synthesized from an unbridged metallocene catalyst is studied using polarimetry. The elastomeric nature of ePP is presumed to arise from a multiblock structure of isotactic (iPP) and atactic (aPP) polypropylene blocks. At lower temperatures stereoregular blocks of iPP are able to crystallize while stereoirregular blocks of aPP remain amorphous. The flow behavior of ePP is compared with homopolymer blends of iPP and aPP that have the same isotactic content as ePP as well as solvent fractions of the parent ePP sample. Step shear strain experiments carried out on crystallized samples show that ePP does not completely relax from an applied strain and that a cross-linked network has formed. Imperfections in the network structure are revealed by birefringence measurements that show a partial relaxation of the polymer orientation. In contrast, crystallized homopolymer blend samples are able to completely relax after the application of a step shear strain. Step shear strain experiments of the solvent fractions of ePP suggest that the elastomeric behavior results from a combination of fractions that are able to cocrystallize to form a physically cross-linked network.
Conclusions (1995)

The aim of this study has been to present a coherent methodology for business cycle research, and to demonstrate its power by applying it to the data of USA and Germany. Here I summarize the major findings as well as some open questions that should be addressed in the future.
A Career in Catalysis: James A. Dumesic (2021)

After 43 years as a professor in the Chemical and Biological Engineering Department at the University of Wisconsin-Madison, James A. Dumesic retired in 2019. Jim is one of the most influential researchers in the field of heterogeneous catalysis. In this Account, we discuss the scientific discoveries that he made and the intellectual processes that he followed during his illustrious career to steer the field of heterogeneous catalysis into new frontiers. He began his career by fundamentally probing the nature of active sites on heterogeneous catalysts using in situ Mössbauer spectroscopy, electron microscopy, FTIR, and kinetic analysis. This tool kit was used to elucidate the “strong metal support interaction” (SMSI) effect. He developed new microcalorimetric tools to measure the energetics of adsorbates on catalyst surfaces. Jim pioneered microkinetic analysis as a tool to describe heterogeneous reaction kinetics incorporating the essential surface chemistry into kinetic analysis, thereby providing a novel strategy for kinetic assisted catalyst design. Density functional theory (DFT) was combined with FTIR and microcalorimetry to elucidate catalytic surface reactions which were then incorporated into microkinetic models. In the early 2000s, Jim developed the aqueous-phase catalytic processing of biomass-derived oxygenates into fuels and chemicals. This led to the development of new processes to make diesel fuel, jet fuel, gasoline, aromatics, and oxygenated chemicals from renewable resources, several of these technologies are in the process of being commercialized. Jim tailored nanostructured catalytic materials by atomic layer deposition and controlled surface reactions to withstand harsh aqueous-phase biomass processing conditions. He used careful selection and tuning of the solvent composition to achieve substantial control over the activity and selectivity of various biomass upgrading reactions and developed a theory to explain these solvent effects. Underlying these discoveries was a thought process that used fundamental surface chemistry to explain the relationship between the structure, properties, and performance of the catalytic system. Leveraging this thought process across many different reaction classes helped to establish both new tools for catalysis research and to develop new processes for the sustainable production of fuels and chemicals.
Photocatalytic degradation of PCP-Na with TiO2 photocatalysis loaded with platinum. (2002)

Titanium dioxide (TiO2) samples of different crystal forms were prepared by hydrolysis tetrabutyl titanate in various water to alkoxide ratios and sintering the hydrolysis product at different temperatures. The photocatalysts coated on hollow glass beads and loaded with platinum varying from 0.2% to 2.4% by weight. The photocatalytic degradation rate of sodium pentachlorophenolate (PCP-Na) depends on the preparing conditions such as: sintering temperatures, water to alkoxide ratios (R), platinum content and the size. The proper conditions of preparation photocatalysts are as follows: the ratio of TiO2: sodium silicate: hollow glass beads: platinum is 10:5:20:0.15 (w/w), R is 100, sintering temperature is 650 degrees C, and the size of hollow glass is 0.5-1 mm. Under these conditions, the ratio between acatase and rutile of the photocatalyst is 2:1, and the photocatalytic activity is high.
Development of high‐concentration lipoplexes for in vivo gene function studies in vertebrate embryos (2011)

Here we report that highly concentrated cationic lipid/helper lipid-nucleic acid complexes (lipoplexes) can facilitate reproducible delivery of a variety of oligonucleotides and plasmids to chicken embryos or to mouse embryonic mesenchyme. Specifically, liposomes composed of N,N-dioleyl-N,N-dimethylammonium chloride (DODAC)/1,2 dioleoyl glycero-3-phosphorylethanolamine (DOPE) prepared at 18-mM concentrations produced high levels of transfection of exogenous genes in vivo and in vitro. Furthermore, we report sufficient uptake of plasmids expressing interference RNA to decrease expression of both exogenous and endogenous genes. The simplicity of preparation, implementation, and relatively low toxicity of this transfection reagent make it an attractive alternative for developmental studies in post-gastrulation vertebrate embryos.
10301 Executive Summary and Abstracts Collection – Service Value Networks (2010)

From 25.07.2010 to 30.07.2010, the Perspectives Workshop 10301 ``Perspectives Workshop: Service Value Networks '' was held in Schloss Dagstuhl~--~Leibniz Center for Informatics. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available.
COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success (2023)

<i>Objective</i>: To determine the target population and optimize the study design of the phase 3 clinical trial evaluating <i>reldesemtiv</i> in participants with amyotrophic lateral sclerosis (ALS).<i>Methods</i>: We evaluated the phase 2 study of <i>reldesemtiv,</i> FORTITUDE-ALS, to inform eligibility criteria and design features that would increase trial efficiency and reduce participant burden of the phase 3 trial.<i>Results</i>: In FORTITUDE-ALS, the effect of <i>reldesemtiv</i> was particularly evident among participants in the intermediate- and fast-progressing tertiles for pre-study disease progression. These participants most often had symptom onset ≤24 months and an ALS Functional Rating Scale-Revised (ALSFRS-R) total score ≤44 at baseline. Compared with the overall FORTITUDE-ALS population, the subgroup meeting these criteria declined by fewer ALSFRS-R points at 12 weeks (difference of least-squares mean [SE] versus placebo 1.84 [0.49] and 0.87 [0.35] for the overall population). These inclusion criteria will be used for the phase 3 clinical trial, COURAGE-ALS, in which the primary outcome is the change in ALSFRS-R total score at week 24. We also measure durable medical equipment use and evaluate strength in muscles expected to change rapidly. To reduce participant burden, study visits are often remote, and strength evaluation is simplified to reduce time and effort.<i>Conclusions</i>: In COURAGE-ALS, the phase 3 clinical trial to evaluate <i>reldesemtiv</i>, the sensitivity of detecting a potential treatment effect may be increased by defining eligibility criteria that limit the proportion of participants who have slower disease progression. Implementing remote visits and simplifying strength measurements will reduce both site and participant burden.ClinicalTrials.gov identifiers: NCT03160898 (FORTITUDE-ALS) and NCT04944784 (COURAGE-ALS).
Effect of Mn doping on charge density in γ-TiAl by quantitative convergent beam electron diffraction (1995)

Abstract The intermetallic compound TiAi with and without 5 at.% manganese, has been studied by energy filtered convergent beam electron diffraction (CBED) in a transmission electron microscope. The addition of Mn is known to be beneficial for the mechanical properties of this material. The aim has been to investigate whether this effect is followed by detectable changes in electronic structure, with the focus on bonding. From the positions of high-order Laue zone lines in the centre disc, the lattice tetragonality is found to decrease with the addition of Mn. By ALCHEMI studies, Mn is found to substitute randomly on Ti and Al sites. The structure factors are determined using multiparameter least-square minimization based on fitting between experimental and calculated intensity profiles. The X-ray structure factors for the nine lowest order reflections have been derived for doped and undoped material. The uncertainty is typically 0·3%, and is best for the strong, lowest order reflections. The electron deformation density maps show that the effect of doping with Mn is to draw charge away from nearest-neighbour covalent bonds and redistribute it more uniformly between second nearest neighbours which may enhance ductility.
INFLAMMATION AND INFLAMMATORY BOWEL DISEASE Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse (2003)

Background and aims: Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. Methods: NEP knockout (NEP2/2) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. Results: Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP2/2 mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP2/2 mice. Infusion of rhNEP to NEP2/2 mice significantly reduced MPO activity 24 hours PI. Conclusions: These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP2/2 mice likely play a role in the earlier onset of intestinal inflammation.
A remote control interface for large displays (2004)

We describe a new widget and interaction technique, known as a "Frisbee," for interacting with areas of a large display that are difficult or impossible to access directly. A frisbee is simply a portal to another part of the display. It consists of a local "telescope" and a remote "target". The remote data surrounded by the target is drawn in the telescope and interactions performed within it are applied on the remote data. In this paper we define the behavior of frisbees, show unique affordances of the widget, and discuss design characteristics. We have implemented a test application and report on an experiment that shows the benefit of using the frisbee on a large display. Our results suggest that the frisbee is preferred over walking back and forth to the local and remote spaces at a distance of 4.5 feet.
A steady-state model for a low-pressure Cs-Ba diode (1993)

A steady-state model of a low-pressure Cs-Ba discharge is developed. It calculates the plasma density, electron temperature, Cs atom densities, and output voltage, assuming uniform conditions across the discharge gap and neglecting radiation losses. The model predictions are in good agreement with experimental data for a low-pressure Cs discharge. Comparing the model to experimental data from a Cs-Ba diode reinforce the validity of the system of equations and also confirms the assumption that barium has practically no effect on the current transport characteristics. The calculated I-V curves for the Cs-Ba diode match well with the experimental data below the emission current; however, above the emission current the calculated currents are much lower. This difference occurs when the model incorporates normal Schottky emission instead of anomalous Schottky. The effect of the latter is determined from estimates of the effective changes in the emitter work function for agreement between the model and experiments at high discharge currents. For such currents, results suggest that changing the Cs pressure strongly affects the anomalous Schottky emission, while changes in the Ba pressure seem to have a negligible effect.
Alterations and Role of Human Cathepsin D inCancer Metastasis (1996)

Cathepsin D (Cath D) overexpression in breast cancer cells is associated with increased risk of metastasis in patients according to several clinical studies. The amino acid sequence of Cath D in two breast cancer cell lines was normal, but glycosylation appears to be different with more acidic isoforms. Transfection of a human cDNA Cath D expression vector increases the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intravenously injected into nude mide. The mechanism of Cath-D-induced metastasis seems to require maturation of the proenzyme, mostly in large acidic compartments identified as phagosomes. Cath D is mitogenic in different cell types, and different substrates (growth inhibitors, precursors of growth factors, etc.) are proposed to mediate this activity.
Comparison of the intracellular itineraries of insulin-like growth factor-I and insulin and their receptors in Rat-1 fibroblasts. (1994)

In this study we have compared the intracellular itineraries of insulin and insulin-like growth factor-I (IGF-I) and their receptors subsequent to ligand internalization in rat fibroblasts. We found that the endocytic rate constant is approximately 3 times as high for insulin as for IGF-I. The dissociation of internalized ligand from its receptor was monitored by the ability of ligand-receptor complexes to precipitate in the presence of polyethylene glycol (PEG). Insulin loses its ability to precipitate with PEG more rapidly than IGF-I. After 60 min, less than 10% of the intracellular insulin remains PEG precipitable, whereas 44% of intracellular IGF-I stays PEG precipitable. Ligand degradation was determined by precipitation with trichloroacetic acid (TCA). Insulin degradation after internalization is more rapid compared with IGF-I degradation; after 2 h, 80% of intracellular IGF-I, in contrast to only 30% of intracellular insulin, remains intact. We measured retroendocytosis of insulin and IGF-I by assessing the amount of internalized ligand that was subsequently released from the cells. When analyzing released ligand by TCA precipitation, we found that 25% of insulin and 53% of IGF-I were TCA precipitable. After 120 min, only 16% of insulin and 43% of IGF-I remained intracellular. To provide insight into a possible mechanism that prevents IGF-I from being subjected to the same degree of degradation as insulin, we studied the effect of pH on IGF-I and insulin binding. We found IGF-I binding to be less sensitive to decreases in pH compared with insulin binding. Therefore, it is likely that after internalization, IGF-I does not dissociate from its intracellular receptor as easily as insulin in the acidifying endosome and, therefore, can return to the cell surface via a recycling receptor. In summary, we have observed distinct differences in the intracellular itineraries of IGF-I and insulin and their receptors. IGF-I internalization and degradation proceed less efficiently than insulin internalization, and IGF-I is preferentially targeted into a retroendocytotic pathway in contrast to insulin, which primarily undergoes lysosomal degradation. The differential effect of pH on ligand binding to these structurally related hormone receptors may account for the quantitatively distinct ligand trafficking events.