1,233 research outputs found

    Synthetic induction of immunogenic cell death by genetic stimulation of endoplasmic reticulum stress.

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    Cis-diamminedichloridoplatinum(II) (CDDP), commonly referred to as cisplatin, is a chemotherapeutic drug used for the treatment of a wide range of solid cancers. CDDP is a relatively poor inducer of immunogenic cell death (ICD), a cell death modality that converts dying cells into a tumor vaccine, stimulating an immune response against residual cancer cells that permits long-lasting immunity and a corresponding reduction in tumor growth. The incapacity of CDDP to trigger ICD is at least partially due to its failure to stimulate the premortem endoplasmic reticulum (ER)-stress response required for the externalization of the "eat-me" signal calreticulin (CRT) on the surface of dying cancer cells. Here, we developed a murine cancer cell line genetically modified to express the ER resident protein reticulon-1c (Rtn-1c) by virtue of tetracycline induction and showed that enforced Rtn-1c expression combined with CDDP treatment promoted CRT externalization to the surface of cancer cells. In contrast to single agent treatments, the tetracycline-mediated Rtn-1c induction combined with CDDP chemotherapy stimulated ICD as measured by the capacity of dying tumor cells, inoculated into syngenic immunocompetent mice, to mount an immune response to tumor re-challenge 1 week later. More importantly, established tumors, forced to constitutively express Rtn-1c in vivo by continuous treatment with tetracycline, became responsive to CDDP and exhibited a corresponding reduction in the rate of tumor growth. The combined therapeutic effects of Rtn-1c induction with CDDP treatment was only detected in the context of an intact immune system and not in nu/nu mice lacking thymus-dependent T lymphocytes. Altogether, these results indicate that the artificial or "synthetic" induction of immunogenic cell death by genetic manipulation of the ER-stress response can improve the efficacy of chemotherapy with CDDP by stimulating anticancer immunity

    Noiseless nonreciprocity in a parametric active device

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    Nonreciprocal devices such as circulators and isolators belong to an important class of microwave components employed in applications like the measurement of mesoscopic circuits at cryogenic temperatures. The measurement protocols usually involve an amplification chain which relies on circulators to separate input and output channels and to suppress backaction from different stages on the sample under test. In these devices the usual reciprocal symmetry of circuits is broken by the phenomenon of Faraday rotation based on magnetic materials and fields. However, magnets are averse to on-chip integration, and magnetic fields are deleterious to delicate superconducting devices. Here we present a new proposal combining two stages of parametric modulation emulating the action of a circulator. It is devoid of magnetic components and suitable for on-chip integration. As the design is free of any dissipative elements and based on reversible operation, the device operates noiselessly, giving it an important advantage over other nonreciprocal active devices for quantum information processing applications.Comment: 17 pages, 4 figures + 12 pages Supplementary Informatio

    Preferential Paths of Air-water Two-phase Flow in Porous Structures with Special Consideration of Channel Thickness Effects.

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    Accurate understanding and predicting the flow paths of immiscible two-phase flow in rocky porous structures are of critical importance for the evaluation of oil or gas recovery and prediction of rock slides caused by gas-liquid flow. A 2D phase field model was established for compressible air-water two-phase flow in heterogenous porous structures. The dynamic characteristics of air-water two-phase interface and preferential paths in porous structures were simulated. The factors affecting the path selection of two-phase flow in porous structures were analyzed. Transparent physical models of complex porous structures were prepared using 3D printing technology. Tracer dye was used to visually observe the flow characteristics and path selection in air-water two-phase displacement experiments. The experimental observations agree with the numerical results used to validate the accuracy of phase field model. The effects of channel thickness on the air-water two-phase flow behavior and paths in porous structures were also analyzed. The results indicate that thick channels can induce secondary air flow paths due to the increase in flow resistance; consequently, the flow distribution is different from that in narrow channels. This study provides a new reference for quantitatively analyzing multi-phase flow and predicting the preferential paths of immiscible fluids in porous structures

    Resource-efficient high-dimensional subspace teleportation with a quantum autoencoder.

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    Quantum autoencoders serve as efficient means for quantum data compression. Here, we propose and demonstrate their use to reduce resource costs for quantum teleportation of subspaces in high-dimensional systems. We use a quantum autoencoder in a compress-teleport-decompress manner and report the first demonstration with qutrits using an integrated photonic platform for future scalability. The key strategy is to compress the dimensionality of input states by erasing redundant information and recover the initial states after chip-to-chip teleportation. Unsupervised machine learning is applied to train the on-chip autoencoder, enabling the compression and teleportation of any state from a high-dimensional subspace. Unknown states are decompressed at a high fidelity (~0.971), obtaining a total teleportation fidelity of ~0.894. Subspace encodings hold great potential as they support enhanced noise robustness and increased coherence. Laying the groundwork for machine learning techniques in quantum systems, our scheme opens previously unidentified paths toward high-dimensional quantum computing and networking

    Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

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    Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at sNN\sqrt{s_{_{\rm NN}}} = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in η<0.8|\eta|<0.8 and 0.3<pT<200.3 < p_T < 20 GeV/cc are compared to the expectation in pp collisions at the same sNN\sqrt{s_{\rm NN}}, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAAR_{\rm AA}. The result indicates only weak medium effects (RAAR_{\rm AA} \approx 0.7) in peripheral collisions. In central collisions, RAAR_{\rm AA} reaches a minimum of about 0.14 at pT=6p_{\rm T}=6-7GeV/cc and increases significantly at larger pTp_{\rm T}. The measured suppression of high-pTp_{\rm T} particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

    Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

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    The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388
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