gebhart/patrepeval huggingface dataset:
Toxicology and Pharmacokinetics of DT<sub>388</sub>IL3, a Fusion Toxin Consisting of a Truncated Diphtheria Toxin (DT<sub>388</sub>) Linked to Human Interleukin 3 (IL3), in Cynomolgus Monkeys (2004)

The fusion toxin DT388IL3 composed of the catalytic and translocation domains of diphtheria toxin (DT388) linked to interleukin-3 (IL3) was administered to 6 cynomolgus monkeys which possessed cross-reactive IL3 receptors. Groups of 2 animals (1 male and 1 female) received up to 6 every other day slow intravenous infusions of 40, 60, or 100 microg/kg DT388IL3. Monkeys given 40 or 60 microg/kg showed mild or moderate transient malaise and anorexia, respectively, without evidence of organ damage by blood tests or histopathology. Animals treated at 100 microg/kg showed severe malaise and anorexia. The female monkey had moderate to severe vasculitis in multiple tissues. Necropsies were performed on the 40 microg/kg monkeys on day 14 and the 100 microg/kg monkeys on days 6 and 7. DT388IL3 plasma half-life was approximately 30 min with a peak concentration of 0.45 microg/ml or 10,000 pM (IC50 for AML blasts treated in vitro was 6 pM). Immune responses were minimal in 4 animals tested at 12 days and 2 animals tested at 30 days post treatment with anti-DT388IL3 levels < 1 microg/ml. Bone marrow aspirates were obtained on all animals at day 19 or at necropsy and revealed myeloid suppression in the females and myeloid hyperplasia in the males irrespective of dose groups. The maximal tolerated dose of 60 microg/kg for 6 doses is markedly higher than other recombinant diphtheria toxins and provides a dose level sufficient for anti-leukemic activity in vitro and in rodent models. Thus, we propose this agent is a promising drug for AML patients.
Aerosol assisted chemical vapour deposition of hydrophobic TiO2–SnO2 composite film with novel microstructure and enhanced photocatalytic activity (2013)

Aerosol assisted chemical vapour deposition (AACVD) was used to synthesise a TiO2–SnO2 composite film onto a glass substrate. For comparison a TiO2 film and a SnO2 film were also prepared. All films were characterised by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and wavelength dispersive X-ray spectroscopy (WDX). XPS and WDX of the composite film revealed a TiO2 rich film with a high level of SnO2 segregation at the surface. Highly structured pyramid-like features gave rise to hydrophobic films with static water contact angles of 134°. Photocatalytic activities were determined by monitoring the degradation of intelligent ink (containing Resazurin redox dye) via UV-visible spectroscopy. Under UVA irradiation, the TiO2 film only began to degrade the dye after being irradiated in excess of 100 minutes, whereas the composite TiO2–SnO2 film required only 6 minutes of irradiation before degradation was observed. The formal quantum efficiency (FQE) for the TiO2–SnO2 composite was determined to be 1.01 × 10−2 molecules per incident photon and the formal quantum yield (FQY) was 1.17 × 10−2 molecules per absorbed photon. This is an order of magnitude superior to Pilkington Activ™ self-cleaning glass a commercial self-cleaning TiO2 coating on glass. This improved photocatalytic activity is attributed to the presence of electron scavenging SnO2 sites that increase charge separation and the increased surface area due to the highly structured morphology.
The P2Y2 nucleotide receptor requires interaction with αv integrins to access and activate G12 (2007)

The P2Y2 nucleotide receptor (P2Y2R) interacts with alpha v integrins to activate G(o) and induce chemotaxis in human 1321N1 astrocytoma cells. In this study, it was determined that the P2Y2R also requires interaction with alpha v integrins to activate G12 and associated signaling pathways that control chemotaxis in 1321N1 cells. Mutation of the Arg-Gly-Asp (RGD) integrin-binding sequence in the first extracellular loop of the human P2Y2R to Arg-Gly-Glu (RGE), which prevents integrin interaction, did not inhibit G(q) or ERK1/2 signaling by the P2Y2R agonist UTP but completely inhibited activation of G12 and G12-mediated events, including Rho activation, cofilin and myosin light chain-2 phosphorylation, stress fiber formation and chemotaxis towards UTP. The involvement of G12 in all these events was verified by using a dominant negative G alpha12 construct. G12 activation by the P2Y2R also was inhibited by anti-alpha v beta5 integrin antibodies and alpha v integrin antisense oligonucleotides, suggesting that alpha v integrin activity and expression are required for the P2Y2R to activate G12. Co-immunoprecipitation experiments confirmed that G alpha12 protein associates with the wild-type P2Y2R and with alpha v integrins but not with the RGE mutant P2Y2R or with alpha3 integrins. Collectively, these results suggest that alpha v integrin complexes provide the P2Y2R with access to G12, thereby allowing activation of this heterotrimeric G protein that controls actin cytoskeletal rearrangements required for chemotaxis.
The stock market implication of political connections: evidence from firms' dividend policy (2012)

Political connections are valuable for shareholders of privately-run firms especially in countries with weak legal institutions. We study the effect of a firm's political connections in the public equity market by focusing on its impact on the firms' dividend policy. Prior studies suggest that dividends signal the commitment for proper treatment of minority shareholders and thus high growth firms pay dividends to establish such a reputation for better access to equity market in the future. Using a sample of privately-owned Chinese firms, we find that politically connected firms are less likely to pay dividends and pay less if they pay. Investors value firms' political connections more than dividends, and they are more likely to endorse managerial decisions in politically connected firms. Specifically, investors of these firms have a significantly lower valuation of dividend payouts than otherwise similar firms but without connections. They prefer firm investments to cash payouts by connected firms with high growth opportunities, and tend to value these firms' investment decisions significantly higher. Finally, connected firms are also more able to tap public equity market for funds. Our study sheds light on the effect of political connections on firm policies.
Exploring non‐linear effects of determinants on tourists' satisfaction (2009)

Purpose The effect of the antecedents of satisfaction on consumer satisfaction is an issue still under debate in the academic literature. Thus, the primary goal of this article is to analyze the relationship between two of the most important antecedents of consumer satisfaction – namely perceived quality and price. Design/methodology/approach To analyze the relationship between tourist consumer satisfaction and its main antecedents, we performed an empirical study on such issues with regard to the purchase of a package tour. Findings The results of this research are that the tourist's perception of quality has a positive and significant effect on his or her satisfaction. This effect is of greater magnitude than the effect produced by perceived price. The present study identifies two components in the total effect of perceived price on satisfaction. Those components have opposite signs: the negative effect of the sacrifice perceived by the consumer and the positive effect that shows the influence of price as a sign of quality. One can estimate the first effect from the price that the consumer recalls paying, which shows a non‐linear negative effect on satisfaction (following the model of “decreasing returns”). One can estimate the positive effect by the range of minimum and maximum prices that the consumer considers acceptable to pay for the product. Originality/value Entrepreneurs must know how improvement in service quality influences customer satisfaction and what price levels they might consider to increase consumer satisfaction and to influence positively the quality perceived by the consumer.
Phloem-sap feeding by animals: problems and solutions (2006)

The incidence of phloem sap feeding by animals appears paradoxical. Although phloem sap is nutrient-rich compared with many other plant products and generally lacking in toxins and feeding deterrents, it is consumed as the dominant or sole diet by a very restricted range of animals, exclusively insects of the order Hemiptera. These insects display two sets of adaptations. First, linked to the high ratio of non-essential:essential amino acids in phloem sap, these insects contain symbiotic micro-organisms which provide them with essential amino acids. For example, bacteria of the genus Buchnera contribute up to 90% of the essential amino acids required by the pea aphid Acyrthosiphon pisum feeding on Vicia faba. Second, the insect tolerance of the very high sugar content and osmotic pressure of phloem sap is promoted by their possession in the gut of sucrase-transglucosidase activity, which transforms excess ingested sugar into long-chain oligosaccharides voided via honeydew. Various other animals consume phloem sap by proxy, through feeding on the honeydew of phloem-feeding hemipterans. Honeydew is physiologically less extreme than phloem sap, with a higher essential:non-essential amino acid ratio and lower osmotic pressure. Even so, ant species strongly dependent on honeydew as food may benefit from nutrients derived from their symbiotic bacteria Blochmannia.
Current status of radiotherapy with proton and light ion beams (2007)

Several model studies have shown potential clinical advantages with charged particles (protons and light ions) compared with 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in many disease sites. The newly developed intensity-modulated proton therapy (IMPT) often yields superior dose distributions to photon IMRT, with the added advantage of a significant reduction in the volume of healthy normal tissues exposed to low-to-medium doses. Initially, the major emphasis in clinical research for proton and light ion therapy was dose escalation for inherently radioresistant tumors, or for lesions adjacent to critical normal structures that constrained the dose that could be safely delivered with conventional x-ray therapy. Since the advent of IMRT the interest in particle therapy has gradually shifted toward protocols aimed at morbidity reduction. Lately the emphasis has mostly been placed on the potential for reduced risk of radiation-induced carcinogenesis with protons. Compared with 3D-CRT, a 2-fold increase has been theoretically estimated with the use of IMRT due to the larger integral volumes. In the pediatric setting, due to a higher inherent susceptibility of tissues, the risk could be significant, and the benefits of protons have been strongly emphasized in the literature. There is a significant expansion of particle therapy facilities around the world. Increasing public awareness of the potential benefits of particle therapy and wider accessibility for patients require that treating physicians stay abreast of the clinical indications of this radiotherapy modality. The article reviews the available literature for various disease sites in which particle therapy has traditionally been considered to offer clinical advantages and to highlight current lines of clinical research. The issue of radiation-induced second malignancies is examined in the light of the controversial epidemiological evidence available. The cost-effectiveness of particle therapy is also discussed.
PVT Variation Tolerant Current Source With On-Chip Digital Self-Calibration (2011)

A current source with a small current error has been proposed to maintain the bandwidth of the system without an increase in power consumption for a margin. It minimizes the current error under process, supply voltage, and temperature (PVT) variations. Because the on-resistance of the nMOS array is self-calibrated digitally by an on-chip digital PVT detector, a current error of only ±2% is achieved. The current source has been implemented in an 80-nm CMOS process, occupies 0.018 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and consumes 94.9 μW at a supply voltage of 1.0 V.
Dynamic strain measurement in optical fibers by stimulated Brillouin scattering (2009)

We present a technique for dynamic strain measurements in optical fibers based on the stimulated Brillouin scattering interaction between two counterpropagating optical pulses. The technique allows for a high sampling rate and permits to addressing dynamically and randomly the position at which vibration is measured. Preliminary experimental results carried out with a perturbation frequency up to 98 Hz demonstrate the validity of the proposed technique.
The structure, modelling and dynamics of hindered 5,6-diarylacenaphthenes (2001)

A series of 5,6-diarylacenaphthenes, 2–4, has been investigated using a variety of theoretical and experimental methods. The purpose of the investigation was to gain a thorough understanding of the dynamics of atropisomer interconversion in these molecules. Quantum chemical calculations were performed at different levels, including Hartree–Fock theory, density functional theory (B3LYP), and a semi-empirical method (AM1). Basis sets used ranged from STO-3G to 6-31+G*. The structures of energy minima and transition states for anti–syn interconversion were fully optimised. A geometrical comparison of the single-crystal X-ray structures of syn-2b, anti-2c and anti-2d was made with the results from the calculations, and revealed excellent agreement in most cases. Theoretical barriers to rotation were compared with those derived experimentally by NMR spectroscopy. Again excellent correlation between theoretical and experimental values was found. In the transition states a significant deviation from planarity for the acenaphthene moiety was calculated. The transition state structures indicate why bulky substituents, such as But, in the 3′ and 3″ positions of the peri-aryl rings are not able to prevent atropisomer interconversion. The structures provide a good explanation for the trends observed in experimental barriers to rotation.
Eternity and functionality – rational access to physiologically relevant cell lines (2013)

In the first 50 years of cell culture, the development of new cell lines was mainly based on trial and error. Due to the understanding of the molecular networks of aging, senescence, proliferation, and adaption by mutation, the generation of new cell lines with physiologic properties has become more systematic. This endeavor has been supported by the availability of new technological achievements and increasing knowledge about the biology of cell differentiation and cell-cell communication. Here, we review some promising developments that are contributing toward this goal. These include molecular tools frequently used for the immortalization process. In addition to these broadly acting immortalization regimens, we focus on the developments of cell type-specific immortalization and on the methodologies of how to control the growth of newly established cell lines.
Increased Levels of NOTCH1, NF-κB, and Other Interconnected Transcription Factors Characterize Primitive Sets of Hematopoietic Stem Cells (2009)

As previously shown, higher levels of NOTCH1 and increased NF-kappaB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency (than expected by chance) of NF-kappaB-binding sites (BS), including potentially novel NF-kappaB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappaB, and other important TFs on more primitive HSC sets.
Conservation, Surface Exposure, and In Vivo Expression of the Frp Family of Iron-Regulated Cell Wall Proteins in <i>Staphylococcus aureus</i> (2002)

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis identified two conserved, immunogenic Staphylococcus aureus cell wall proteins, of 40 and 87 kDa, expressed under iron-restricted growth conditions in vitro and in vivo. N-terminal sequencing and subsequent genome analysis showed that these proteins are encoded by adjacent monocistronic open reading frames designated frpA and frpB, respectively. Studies with an S. aureus fur mutant confirmed that expression of FrpA and FrpB is regulated by Fur but that there also appears to be differential expression of these proteins in different iron-restricted media in vitro. FrpA and FrpB share some amino acid sequence homology with each other and with a putative S. aureus membrane protein, FrpC. frpC is the first gene of a Fur-regulated operon encoding four proteins of unknown function (FrpC, -D, -G, and -H) and the binding protein (FrpE) and permease (FrpF) of a putative iron transporter. Antisense mutagenesis and bioassays showed that FrpA and FrpB are not required for growth of S. aureus under iron-restricted conditions in vitro and do not appear to be involved in the transport of iron from siderophores or in binding of hemin. Further phenotypic analysis suggested that FrpA may be involved in adhesion of S. aureus to plastic in vitro. Binding of S. aureus to microtiter wells was found to be iron regulated, and iron-restricted S. aureus containing antisense frpA or frpAB but not frpB constructs showed reduced binding compared to vector construct controls.
β2 integrin mediates hantavirus-induced release of neutrophil extracellular traps (2014)

Rodent-borne hantaviruses are emerging human pathogens that cause severe human disease. The underlying mechanisms are not well understood, as hantaviruses replicate in endothelial and epithelial cells without causing any cytopathic effect. We demonstrate that hantaviruses strongly stimulated neutrophils to release neutrophil extracellular traps (NETs). Hantavirus infection induced high systemic levels of circulating NETs in patients and this systemic NET overflow was accompanied by production of autoantibodies to nuclear antigens. Analysis of the responsible mechanism using neutrophils from β2 null mice identified β2 integrin receptors as a master switch for NET induction. Further experiments suggested that β2 integrin receptors such as complement receptor 3 (CR3) and 4 (CR4) may act as novel hantavirus entry receptors. Using adenoviruses, we confirmed that viral interaction with β2 integrin induced strong NET formation. Collectively, β2 integrin-mediated systemic NET overflow is a novel viral mechanism of immunopathology that may be responsible for characteristic aspects of hantavirus-associated disease such as kidney and lung damage.
Development of ratiometric near-infrared fluorescent probes using analyte-specific cleavage of carbamate (2013)

We report a facile method to design NIR ratiometric fluorescent probes in terms of analyte-induced carbamate cleavage. Two examples, CyNB and CyNN3, exhibit a significant analyte-triggered response with ratiometric fluorescence change in the NIR range and dual-emission ratiometry in living cells.
Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation (2020)

Regulation of the peripheral vascular resistance via modulating the vessel diameter has been considered as a main determinant of the arterial blood pressure. Phosphodiesterase enzymes (PDE1-11) hydrolyse cyclic nucleotides, which are key players controlling the vessel diameter and, thus, peripheral resistance. Here, we have tested and reported the effects of a novel selective PDE1 inhibitor (BTTQ) on the cardiovascular system. Normal Sprague Dawley, spontaneously hypertensive (SHR), and Dahl salt-sensitive rats were used to test <i>in vivo</i> the efficacy of the compound. Phosphodiesterase radiometric enzyme assay revealed that BTTQ inhibited all three isoforms of PDE1 in nanomolar concentration, while micromolar concentrations were needed to induce effective inhibition for other PDEs. The myography study conducted on mesenteric arteries revealed a potent vasodilatory effect of the drug, which was confirmed <i>in vivo</i> by an increase in the blood flow in the rat ear arteriols reflected by the rise in the temperature. Furthermore, BTTQ proved a high efficacy in lowering the blood pressure about 9, 36, and 24 mmHg in normal Sprague Dawley, SHR and, Dahl salt-sensitive rats, respectively, compared to the vehicle-treated group. Moreover, additional blood pressure lowering of about 22 mmHg could be achieved when BTTQ was administered on top of ACE inhibitor lisinopril, a current standard of care in the treatment of hypertension. Therefore, PDE1 inhibition induced efficient vasodilation that was accompanied by a significant reduction of blood pressure in different hypertensive rat models. Administration of BTTQ was also associated with increased heart rate in both models of hypertension as well as in the normotensive rats. Thus, PDE1 appears to be an attractive therapeutic target for the treatment of resistant hypertension, while tachycardia needs to be addressed by further compound structural optimization.
Opportunities for casualty reduction in rollover crashes (1995)

This paper applies on-the-road crash data and computer modelling to clarify opportunities for reducing rollover crash casualties. Countermeasures to reduce rollover casualties include increased belt use, and technological interventions to prevent ejection and to reduce the severity of body contacts with the vehicle interior. The vehicle speed immediately prior to the rollover is a pivotal predictor of rollover crash severity. The number of vehicle quarter turns, the vehicle damage, and the roll rate are also predictors, and are strongly related to the initial vehicle speed. Computer simulators described suggest that the severity of the tripping acceleration may also have a strong influence on occupant ejections and injuries. (A) For the covering abstract of the conference see IRRD 894848.