gebhart/patrepeval huggingface dataset:
Differential Cross-regulation of the Human Chemokine Receptors CXCR1 and CXCR2 (1998)

Neutrophils and transfected RBL-2H3 cells were used to investigate the mechanism of cross-regulation of the human interleukin-8 (IL-8) receptors CXCR1 and CXCR2 by chemoattractants. In neutrophils, Ca2+ mobilization by the CXCR2-specific chemokine, growth-related oncogene alpha (Groalpha), was desensitized by prior exposure to the chemoattractants N-formylated peptides (fMLP) or a complement cleavage product (C5a). In contrast, growth-related oncogene alpha did not desensitize the latter receptors. To investigate this phenomenon, CXCR2 was stably expressed in RBL-2H3 cells and mediated phosphoinositide hydrolysis, Ca2+ mobilization, chemotaxis, and secretion. In cells co-expressing CXCR2 and receptors for either C5a (C5aR) or fMLP (FR), CXCR2 was cross-phosphorylated and cross-desensitized by C5a and fMLP. However, neither C5aR nor FR was cross-phosphorylated or cross-desensitized by CXCR2 activation, although CXCR1 did mediate this process. Receptor internalization induced by IL-8 was more rapid and occurred at lower doses with CXCR2 than CXCR1, although both receptors mediated equipotent chemotaxis and exocytosis in RBL. Truncation of the cytoplasmic tail of CXCR2 (331T) prolonged its signaling relative to CXCR2, increased its resistance to internalization, and induced phospholipase D activation. 331T was resistant to homologous phosphorylation and cross-phosphorylation but not cross-desensitization of its Ca2+ mobilization by fMLP or C5a, indicating an inhibitory site distal to receptor/G protein coupling. In contrast to CXCR2, stimulation of 331T cross-desensitized Ca2+ mobilization by both FR and C5aR. CXCR2 and the mutant 331T induced phospholipase C beta3 phosphorylation to an extent equivalent to that of CXCR1. Taken together, these results suggest that CXCR1 and CXCR2 bind IL-8 to produce a group of equipotent responses, but their ability to generate other signals, including receptor internalization, cross-desensitization, and phospholipase D activation, are very different. The latter phenomena apparently require prolonged receptor activation, which in the case of CXCR2 is precluded by rapid receptor phosphorylation and internalization. Thus, receptors coupling to identical G proteins may trigger different cellular responses dependent on the length of their signaling time, which can be regulated by receptor phosphorylation.
Mechanisms of transfusion-related acute lung injury (TRALI): Anti-leukocyte antibodies (2006)

There is abundant evidence that leukocyte antibodies in blood donor products are somehow involved in transfusion-related acute lung injury (TRALI). Human leukocyte antigen (HLA) class I, HLA class II, and neutrophil-specific antibodies in the plasma of both blood donors and recipients have been implicated in the pathogenesis of TRALI. The case for a relationship between leukocyte antibodies and TRALI is more compelling if concordance between the antigen specificity of the leukocyte antibodies in the donor plasma and the corresponding antigen on the cells of the affected recipient is demonstrated. Such antibody-antigen concordance can be investigated by typing the recipient for the cognate leukocyte antigens or by cross-matching the donor plasma against the recipient's leukocytes. Two proposed pathophysiologic mechanisms for TRALI have received the most attention: the antibody hypothesis and the two-event hypothesis. The final common pathway in all of the proposed pathogenic mechanisms of TRALI is increased pulmonary capillary permeability, which results in movement of plasma into the alveolar space causing pulmonary edema. A typical TRALI serologic workup consists of tests for HLA class I and II and neutrophil-specific antibodies. The use of flow cytometry and HLA-coated microbeads is recommended for detection of HLA antibodies in plasma of implicated blood donors and a combination of the granulocyte agglutination test and granulocyte immunofluorescence test for detection of neutrophil-specific antibodies. Genotyping for class I and II HLA and for a limited number of neutrophil antigens may also be helpful in establishing antibody-antigen concordance.
Reversion of Human Pgp-Dependent Multidrug Resistance by New Sesquiterpenes from Zinowiewia costaricensis (2005)

In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C NMR spectroscopic studies, including homonuclear and heteronuclear correlation experiments. The absolute configurations of the new compounds were determined by CD studies, chemical correlations or biogenetic grounds. All the natural compounds and derivative 20 have been tested on human MDR1-transfected NIH-3T3 cells, to determine their ability to revert the multidrug resistance phenotype due to P-glycoprotein overexpression. Six compounds from this series (1, 8, 11, 12, 13 and 14) showed similar effectiveness to the classical P-glycoprotein modulator verapamil when reversing resistance to daunorubicin, but it is up to sixteen times greater than that of verapamil when reversing resistance to vinblastine. The structure-activity relationships are discussed.
The Constrained CramÉr–Rao Bound From the Perspective of Fitting a Model (2007)

Stoica and Ng (1998) presented a simple expression for the constrained Cramer-Rao bound (CCRB) when the constraints are given by a differentiable function of the parameter to be estimated. This letter considers the parallel case in developing the CCRB when the parameters are locally fitted to a lower-dimensional parametric model, i.e., the parameters are locally assumed to be functions of a distinct reduced parameter vector. We employ classical elements of CRB theory on the locally fitted model to present a very simple derivation of the CCRB, conditions for attaining the bound, and a regularity condition. Examples illustrate the key ideas.
An AI Planning Approach for Generating Big Data Workflows (2015)

The scale of big data causes the compositions of extract-transform-load (ETL) workflows to grow increasingly complex. With the turnaround time for delivering solutions becoming a greater emphasis, stakeholders cannot continue to afford to wait the hundreds of hours it takes for domain experts to manually compose a workflow solution. This paper describes a novel AI planning approach that facilitates rapid composition and maintenance of ETL workflows. The workflow engine is evaluated on real-world scenarios from an industrial partner and results gathered from a prototype are reported to demonstrate the validity of the approach.
A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast growth factor 2-dependent angiogenesis. (2002)

Fucosylated chondroitin sulfate (FucCS), a glycosaminoglycan obtained from sea cucumber, has the same structure as mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. This new polysaccharide has a more favorable effect than heparin on vascular cell growth. It inhibits smooth muscle cell proliferation as heparin, and it has a potent enhancing effect on endothelial cell proliferation and migration in the presence of heparin-binding growth factors. We now extend our studies to the effect of this glycosaminoglycan on endothelial cells to an in vitro angiogenesis model on Matrigel. FucCS, in the presence of fibroblast growth factor-2 (FGF-2), strongly increases the capacity of endothelial cells to form vascular tubes on Matrigel with a well-organized capillary-like network and typical closed structures. Comparison between the activity of native and chemically modified chondroitin sulfate from sea cucumber reveals that the sulfated fucose branches are the structural motif for the proangiogenic activity. Heparin does not induce angiogenesis in this experimental model. We also have evidence for the proposition that endothelial cell proliferation is not the sole event involved in the in vitro FGF-2-induced angiogenesis. It implies a variety of other modifications of the endothelial cells and of their interaction with the extracellular matrix, such as integrin expression and actin cytoskeleton reorganization. Finally, the proangiogenic effect of FucCS, concomitant with its capacity to prevent venous and arterial thrombosis, in animal models makes this new glycosaminoglycan a promising molecule with possible beneficial effects in pathological conditions affecting blood vessels such as the neovascularization of ischemic areas.
1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: A Novel Series of Potent Calcium-Sensing Receptor Antagonists (2010)

Parathyroid hormone (PTH) is an effective bone anabolic agent. However, only when administered by daily sc injections exposure of short duration is achieved, a prerequisite for an anabolic response. Instead of applying exogenous PTH, mobilization of endogenous stores of the hormone can be envisaged. The secretion of PTH stored in the parathyroid glands is mediated by a calcium sensing receptor (CaSR) a GPCR localized at the cell surface. Antagonists of CaSR (calcilytics) mimic a state of hypocalcaemia and stimulate PTH release to the bloodstream. Screening of the internal compound collection for inhibition of CaSR signaling function afforded 2a. In vitro potency could be improved >1000 fold by optimization of its chemical structure. The binding mode of our compounds was predicted based on molecular modeling and confirmed by testing with mutated receptors. While the compounds readily induced PTH release after iv application a special formulation was needed for oral activity. The required profile was achieved by using microemulsions. Excellent PK/PD correlation was found in rats and dogs. High levels of PTH were reached in plasma within minutes which reverted to baseline in about 1-2 h in both species.
Widely changing probability of surface damage creation induced by a single ion in the MeV ion energy range (1998)

We report widely changing probability of surface damage creation induced by a single ion on highly oriented pyrolytic graphite specimens, each implanted with 3.1 MeV Si, Cu, As, Sr, Ag, or Au ions at a dose of 1.9×1011 cm−2. By using a friction force microscope, we observed lattice disordered surface damage, and found the probability of surface damage creation varying from 0.02 to 0.54 depending on the variation in the ion species. To determine the reason for the larger dependence on ion species, we calculated the probabilities of knock-on atom generation by nuclear collision. The calculated probability of knock-on atom generation agreed well with the observed probability of surface damage creation.
Pharmacological treatment in moderate-to-severe Alzheimer's disease (2008)

Pharmacological treatment of moderate-to-severe AD patients can be beneficial. However, cost-benefit data are limited, and the long-term effects and the optimal duration of treatment as patients continue to progress to more severe stages are unknown and require further investigation.
Implementation of a 3D porcine lumbar finite element model for the simulation of monolithic spinal rods with variable flexural stiffness (2015)

Monolithic superelastic-elastoplastic spinal rods (MSER) are promising candidates to provide (i) dynamic stabilisation in spinal segments prone to mechanical stress concentration and adjacent segment disease and (ii) to provide fusion-ready stabilization in spinal segments at risk of implant failure. However, the stiffness distributions along the rod's longitudinal axis that best meet clinical requirements remain unknown. The present study is part of a mixed numerical experimental research project and aims at the implementation of a 3D finite element model of the porcine lumbar spine to study the role of MSER material properties and stiffness distributions on the intradiscal pressure distribution in the adjacent segment. In this paper, preliminary intradiscal pressure predictions obtained at one functional spinal unit are presented. Due to a lack of porcine material property data, these predictions were obtained on the basis of uncalibrated human vertebral disc data which were taken from the literature. The results indicate that human annulus and nucleus data predict experimental porcine in vivo and in vitro data reasonably well for the compressive forces of varying magnitudes.
Evidence for B+ -> J/yp.hivin.L and search for B0 -> J/yp.hivin.p. (2003)

A randomized and prospective study was designed to prove the efficacy of angiotensin II receptor blockers (ARB) in the amelioration of myocardial impairment in hypertrophic nonobstructive cardiomyopathy (HNCM). Nineteen consecutive patients with HNCM were randomly assigned to two groups and then underwent cine magnetic resonance evaluation of left ventricular mass (LVM) twice just before and after one year of observation. In the ARB group, 50 mg of losartan potassium was administered once daily during the observation period. The ratio of LVM after the observation period over that before the period was blindly compared between the two groups to estimate morphologically the ameliorative effect of ARB. In the ARB group, LVM was 203 +/- 47 cm(3) before the treatment period and 190 +/- 55 cm(3) after the period and the ratio of the final LVM over the initial LVM was 0.93 +/- 0.10. In the non-ARB group the initial and final LVM values were 177 +/- 48 cm(3) and 179 +/- 45 cm(3), and the ratio of the final LVM over the initial LVM was 1.02 +/- 0.07. The ratio of the final LVM over the initial LVM in the ARB group was significantly smaller (P = 0.03) than that in the non-ARB group. The smaller ratio in the ARB group strongly indicates that ARB ameliorated the natural course of HNCM during the one year observation period. Thus, this is the first demonstration of the therapeutic efficacy of ARB in human HNCM.
INFRARED THERMOGRAPHY FOR DETECTING DEFECTS IN CONCRETE STRUCTURES (2018)

The traditional methods for inspecting large concrete structures such as dams and cooling towers require erecting large amounts of scaffolding to access the surface of the concrete structure in order to sound the concrete with an impact device or hammer to expose the damaged or defective areas. Another method for accessing the surface of a large concrete structure is to employ climbing inspections which poses a considerable safety risk. These traditional methods are used to determine defect or damage within a few inches of the surface. In addition to the logistic difficulty of these methods a hammer can cause damage if care is not taken. Further, it can cover only a small area. Infrared Thermography (IRT), also referred to as thermal imaging, utilizes the infrared spectrum to show differences in heat dissipating from a structure using a thermal imaging camera. This paper presents a review of the IRT research for detecting defects in concrete structures. Health monitoring and damage detection of large structures such as bridges and high-rise buildings has been a very active area of research in recent years. The two main approaches explored by researchers are vibration-based health monitoring and camera-based vision technology. IRT remains to be another promising technology for economical health monitoring of structures.
Respected Sir(2): magic target for diabetes. (2008)

The endless quest for the 'fountain of youth' has led to the discovery of a family of molecules known as sirtuins in humans, or silent mating type information regulator 2 (Sir2) in yeast, which are associated with longevity in yeast, nematodes, drosophila and rodents. Although sirtuins have yet to be proven to delay aging and promote longevity in humans, they promise 'healthy aging', an ideal of modern society. This review emphasizes the role of various sirtuins in maintaining glucose homeostasis, the therapeutic potential of sirtuin modulators in the prevention and treatment of diabetes, and the emerging associations of SIRT genetic polymorphisms with human longevity.
A 24 GHz low power VCO with transformer feedback (2009)

A K-band low power VCO fabricated by 0.13 µm CMOS technology is developed. By employing a NMOS cross-coupled pair with a transformer feedback, low phase noise under low dc power condition can be achieved at higher frequency. The VCO exhibits a 2.2 GHz frequency tuning range. The output power and the phase noise at 1 MHz offset are −10 dBm and −113 dBc/Hz, respectively. The dc power consumption is 0.6 V/3 mW. To author's knowledge, this performance achieves the best FOM in CMOS K-band VCOs.
Observational Needs Supporting Marine Ecosystems Modeling and Forecasting: From the Global Ocean to Regional and Coastal Systems (2019)

Many coastal areas host rich marine ecosystems and are also centers of economic activities, including fishing, shipping and recreation. Due to the socioeconomic and ecological importance of these areas, predicting relevant indicators of the ecosystem state on sub-seasonal to interannual timescales is gaining increasing attention. Depending on the application, forecasts may be sought for variables and indicators spanning physics (e.g., sea level, temperature, currents), chemistry (e.g., nutrients, oxygen, pH), and biology (from viruses to top predators). Many components of the marine ecosystem are known to be influenced by leading modes of climate variability, which provide a physical basis for predictability. However, prediction capabilities remain limited by the lack of a clear understanding of the physical and biological processes involved, as well as by insufficient observations for forecast initialization and verification. The situation is further complicated by the influence of climate change on ocean conditions along coastal areas, including sea level rise, increased stratification, and shoaling of oxygen minimum zones. Observations are thus vital to all aspects of marine forecasting: statistical and/or dynamical model development, forecast initialization, and forecast validation, each of which has different observational requirements, which may be also specific to the study region. Here, we use examples from United States (U.S.) coasts applications to identify and describe the key requirements for an observational network that is needed to facilitate improved process understanding, as well as for sustaining operational ecosystem forecasting. We also describe new holistic observational approaches, e.g., approaches based on acoustics, inspired by Tara Oceans or by landscape ecology, that have the potential to support and expand ecosystem modeling and forecasting activities by bridging global and local observations.
Probing the Influence of Dielectric Environment upon Volume-Confined Hyperbolic Polaritons (2019)

We employ nano-scale imaging and spectroscopy techniques to elucidate polariton characteristics as a function of the complex refractive index of the substrate. Although higher-order polariton modes exhibit wavelengths weakly sensitive to the environment, the principal mode strongly depends on the substrate dielectric constant.
Upper Bounds for Newton’s Method on Monotone Polynomial Systems, and P-Time Model Checking of Probabilistic One-Counter Automata (2015)

A central computational problem for analyzing and model checking various classes of infinite-state recursive probabilistic systems (including quasi-birth-death processes, multitype branching processes, stochastic context-free grammars, probabilistic pushdown automata and recursive Markov chains) is the computation of termination probabilities, and computing these probabilities in turn boils down to computing the least fixed point (LFP) solution of a corresponding monotone polynomial system (MPS) of equations, denoted x = P ( x ). It was shown in Etessami and Yannakakis [2009] that a decomposed variant of Newton’s method converges monotonically to the LFP solution for any MPS that has a nonnegative solution. Subsequently, Esparza et al. [2010] obtained upper bounds on the convergence rate of Newton’s method for certain classes of MPSs. More recently, better upper bounds have been obtained for special classes of MPSs [Etessami et al. 2010, 2012]. However, prior to this article, for arbitrary (not necessarily strongly connected) MPSs, no upper bounds at all were known on the convergence rate of Newton’s method as a function of the encoding size |P| of the input MPS, x = P ( x ). In this article, we provide worst-case upper bounds, as a function of both the input encoding size |P|, and ε &gt; 0, on the number of iterations required for decomposed Newton’s method (even with rounding) to converge to within additive error ε &gt; 0 of q*, for an arbitrary MPS with LFP solution q*. Our upper bounds are essentially optimal in terms of several important parameters of the problem. Using our upper bounds, and building on prior work, we obtain the first P-time algorithm (in the standard Turing model of computation) for quantitative model checking, to within arbitrary desired precision, of discrete-time QBDs and (equivalently) probabilistic 1-counter automata, with respect to any (fixed) ω -regular or LTL property.
The immunological generation of a platelet-activating factor and a platet-lytic factor in the rat. (1979)

Antigen challenge of the rat peritoneal cavity which had been prepared with IgGa-rich antiserum generated activities which released [14C]-serotonin from pre-labelled human platelets. After adsorption of these activities onto Amberlite XAD-8 and elution in 80% ethanol, two factors of differing polarity were resolved by chromatography on diethylaminoethyl cellulose in organic solvents. The activity eluting in the 7:1 chloroform:methanol solvent contained a platelet-lytic factor (PLF) assessed by the parallel release of lactic acid dehydrogenase and [14C]-serotonin; the cytotoxicity of this fraction was confirmed by phase-contrast microscopy examination which demonstrated fragmentation of the exposed platelets. The activity eluting in the 1:1 methanol: aqueous 1.0 M ammonium carbonate solvent was a platelet-activating factor (PAF) as defined by release of [14C]-serotonin without lactic acid dehydrogenase. Both the lytic and the activating principles were separable from slow reacting substance of anaphylaxis and polymorphonuclear leucocyte chemotactic activity, and each presented a single activity peak of differing mobility when chromatographed on silica gel H plates. Human eosinophil phospholipase D inactivated the lytic factor by more than 85% in 2 h at 37 degrees without affecting the activity of the activating factor. The release of [14C]-serotonin induced by the PAF was not affected by the absence of calcium from the medium or by elevations in the platelet concentrations of cyclic AMP or cyclic GMP that resulted from pre-incubation of platelets with prostaglandin D2 or sodium ascorbate, respectively.