12 research outputs found

    The Utopian Quest: A Visual and Cultural Exploration of Ideal Lands

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    This thesis explores the concept of utopia across different cultures, analyzing the ideal lands in Eastern and Western societies. The author categorizes utopian ideals into two types: Thomas More-style utopias, which aim for social and political perfection, and Arcadian ideals, which prioritize individual inner peace and escape from society. The author compares the ways of entering, the environments, the lifestyles, and the consequences of leaving mentioned in these stories to identify the visual language involved. These visual elements of ideal lands provide a solid foundation for the author\u27s visual thesis, a video game that allows players to build their own ideal world. Overall, this paper highlights the universal human desire for a perfect world and the various cultural expressions of that desire while offering the author\u27s own answer to the ideal land

    Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

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    <p>Abstract</p> <p>Background</p> <p>The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X<sub>7 </sub>receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X<sub>7 </sub>system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X<sub>7 </sub>action.</p> <p>Methods</p> <p>Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X<sub>7</sub>-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X<sub>7 </sub>pore formation) were determined by confocal laser microscopy.</p> <p>Results</p> <p>(a) Co-application on the skin of the P2X<sub>7 </sub>specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X<sub>7</sub>-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X<sub>7 </sub>receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X<sub>7 </sub>receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.</p> <p>Conclusion</p> <p>(a) P2X<sub>7</sub>-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X<sub>7</sub>-dependent apoptosis is mediated by calcium influx via P2X<sub>7 </sub>pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X<sub>7 </sub>receptor. (d) Activation of P2X<sub>7</sub>-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.</p

    Search for light dark matter from atmosphere in PandaX-4T

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    We report a search for light dark matter produced through the cascading decay of η\eta mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne⋅\cdotyear exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at 5.9×10−37cm25.9 \times 10^{-37}{\rm cm^2} for dark matter mass of 0.10.1 MeV/c2/c^2 and mediator mass of 300 MeV/c2/c^2. The lowest upper limit of η\eta to dark matter decay branching ratio is 1.6×10−71.6 \times 10^{-7}

    A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

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    We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c2^2

    High-Temperature Cracking of Pentene to Ethylene and Propylene over H-ZSM-5 Zeolites: Effect of Reaction Conditions and Mechanistic Insights

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    The effects of reaction conditions on the yield of ethylene and propylene from pentene cracking were investigated in a fixed-bed reactor at 500–750 °C and for a weight hourly space velocity (WHSV) of 15–83 h−1. The total yield of ethylene and propylene reached a maximum (67.8 wt%) at 700 °C and 57 h−1. In order to explore the reaction mechanism at high temperatures, a thermal/catalytic cracking proportion model was established. It was found that the proportion of pentene feed chemically adsorbed with the acid sites and cracked through catalytic cracking was above 88.4%, even at 750 °C. Ethylene and propylene in the products were mainly derived from catalytic cracking rather than thermal cracking at 650–750 °C. In addition, the suitable reaction network for pentene catalytic cracking was deduced and estimated. The results showed that the monomolecular cracking proportion increased from 1% at 500 °C to 95% at 750 °C. The high selectivity of ethylene and propylene at high temperatures was mainly due to the intensification of the monomolecular cracking reaction. After 20 times of regeneration, the acidity and pore structure of the zeolite had hardly changed, and the conversion of pentene remained above 80% at 650 °C

    Calibration of a Micromegas-based Gaseous Time Projection Chamber Using Cosmic Ray Muons

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    We report the calibration of a gaseous Time Projection Chamber based on Micromegas charge readout modules with cosmic ray muons, utilizing their penetrating power and relatively uniform energy deposition per unit length. Muon events were selected through track reconstruction to characterize detector performances, such as the drift velocity, electron lifetime, detector gain, and electric field distortion. The evolution of detector performances with gas purities and electric drift fields over a 50-day data-taking cycle was measured by the muon calibration method. For instance, the drift velocity degraded with gas impurities from 3.40±0.07 cm/μs{3.40\pm 0.07 ~ cm/\mu s} to 3.06±0.06 cm/μs{3.06\pm 0.06 ~ cm/\mu s}, and then recovered with gas purification. A 137Cs{^{137}Cs} calibration source was also placed inside the detector as a reference for muon calibrations

    Peptide ligands that use a novel binding site to target both TGF-β receptors

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    The transforming growth factor β (TGF-β) signaling pathway plays myriad roles in development and disease. TGF-β isoforms initiate signaling by organizing their cell surface receptors TβRI and TβRII. Exploration and exploitation of the versatility of TGF-β signaling requires enhanced understanding of structure–function relationships in this pathway. To this end, small molecule, peptide, and antibody effectors that bind key signaling components would serve as valuable probes. We focused on TβRI-ED as a target for effector screening. The observation that the extracellular domain of TβRI (TβRI-ED) can bind to a TGF-β coreceptor (endoglin), suggests that the TβRI-ED may have multiple interaction sites. Using phage display, we identified two peptides LTGKNFPMFHRN (Pep1) and MHRMPSFLPTTL (Pep2) that bind the TβRI-ED (K(d) ~10(-5) M). Although our screen focused on TβRI-ED, the hit peptides interact with the TβRII-ED with similar affinities. The peptide ligands occupy the same binding sites on TβRI and TβRII, as demonstrated by their ability to compete with each other for receptor binding. Moreover, neither interferes with TGF-β binding. These results indicate that TβRI and TβRII both possess hot spots for protein–protein interactions that are distinct from those used by their known ligand TGF-β. To convert these compounds into high affinity probes, we exploited the observation that TβRI and TβRII exist as dimers on the cell surface; therefore, we assembled a multivalent ligand. Specifically, we displayed one of our receptor-binding peptides on a dendrimer scaffold. We anticipate that the potent multivalent ligand that resulted can be used to probe the role of receptor assembly in TGF-β function

    Determination of Double Beta Decay Half-Life of 136Xe with the PandaX-4T Natural Xenon Detector

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    Precise measurement of two-neutrino double beta decay (DBD) half-life is an important step for the searches of Majorana neutrinos with neutrinoless double beta decay. We report the measurement of DBD half-life of 136Xe using the PandaX-4T dual-phase Time Projection Chamber (TPC) with 3.7-tonne natural xenon and the first 94.9-day physics data release. The background model in the fiducial volume is well constrained in situ by events in the outer active region. With a 136Xe exposure of 15.5 kg-year, we establish the half-life as 2.27±0.03stat.±0.10syst.×1021 years. This is the first DBD half-life measurement with natural xenon and demonstrates the physics capability of a large-scale liquid xenon TPC in the field of rare event searches
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