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  • 1
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    Asphalt volcanism and chemosynthetic life, Campeche Knoll, Gulf of Mexico (2004)
    American Association for the Advancement of Science (AAAS)
    In:  Science, 304 . pp. 999-1002.
    Details
    Publication Date: 2016-09-09
    Description: In the Campeche Knolls, in the southern Gulf of Mexico, lava-like flows of solidified asphalt cover more than 1 square kilometer of the rim of a dissected salt dome at a depth of 3000 meters below sea level. Chemosynthetic tubeworms and bivalves colonize the sea floor near the asphalt, which chilled and contracted after discharge. The site also includes oil seeps, gas hydrate deposits, locally anoxic sediments, and slabs of authigenic carbonate. Asphalt volcanism creates a habitat for chemosynthetic life that may be widespread at great depth in the Gulf of Mexico.
    Type: Article , PeerReviewed
    Format: text
    DOI: 10.1126/science.1097154
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    OceanRep: Article in a Scientific Journal - peer-reviewed
  • 2
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    Netrin-1 Induces Medulloblastoma Invasion and Angiogenesis (2014)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2014-07-16
    Description: Invasion and dissemination of medulloblastoma within the central nervous system is the principal factor predicting medulloblastoma treatment failure and death. Netrin-1 is an axon guidance factor implicated in tumor and vascular biology, including in invasive behaviors. We found that exogenous netrin-1 stimulated invasion of human medulloblastoma cells and endothelial cells in contrast to VEGF-A, which promoted invasion of endothelial cells but not medulloblastoma cells. Furthermore, medulloblastoma cells expressed endogenous netrin-1 along with its receptors, neogenin and UNC5B. Blockades in endogenous netrin-1, neogenin, or UNC5B reduced medulloblastoma invasiveness. Neogenin blockade inhibited netrin-1–induced endothelial cells tube formation and recruitment of endothelial cells into Matrigel plugs, two hallmarks of angiogenesis. In patients with pediatric medulloblastoma, netrin-1 mRNA levels were increased 1.7-fold in medulloblastoma tumor specimens compared with control specimens from the same patient. Immunohistochemical analyses showed that netrin-1 was elevated in medulloblastoma tumors versus cerebellum controls. Notably, urinary levels of netrin-1 were 9-fold higher in patients with medulloblastoma compared with control individuals. Moreover, urinary netrin-1 levels were higher in patients with invasive medulloblastoma compared with patients with noninvasive medulloblastoma. Finally, we noted that urinary netrin-1 levels diminished after medulloblastoma resection in patients. Our results suggest netrin-1 is a candidate biomarker capable of detecting an invasive, disseminated phenotype in patients with medulloblastoma and predicting their disease status. Cancer Res; 74(14); 3716–26. ©2014 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 3
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    Favoring the unfavored: Selective electrochemical nitrogen fixation using a reticular chemistry approach (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-03-12
    Description: Electrochemical nitrogen-to-ammonia fixation is emerging as a sustainable strategy to tackle the hydrogen- and energy-intensive operations by Haber-Bosch process for ammonia production. However, current electrochemical nitrogen reduction reaction (NRR) progress is impeded by overwhelming competition from the hydrogen evolution reaction (HER) across all traditional NRR catalysts and the requirement for elevated temperature/pressure. We achieve both excellent NRR selectivity (~90%) and a significant boost to Faradic efficiency by 10 percentage points even at ambient operations by coating a superhydrophobic metal-organic framework (MOF) layer over the NRR electrocatalyst. Our reticular chemistry approach exploits MOF’s water-repelling and molecular-concentrating effects to overcome HER-imposed bottlenecks, uncovering the unprecedented electrochemical features of NRR critical for future theoretical studies. By favoring the originally unfavored NRR, we envisage our electrocatalytic design as a starting point for high-performance nitrogen-to-ammonia electroconversion directly from water vapor–abundant air to address increasing global demand of ammonia in (bio)chemical and energy industries.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor-Modified T Cells Engineered to Secrete Checkpoint Inhibitors (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2017-11-16
    Description: Purpose: Despite favorable responses of chimeric antigen receptor (CAR)-engineered T-cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR T cells secreting checkpoint inhibitors (CPI) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. Experimental Design: To evaluate the effector function and expansion capacity of CAR.αPD1-T cells in vitro , we measured the production of IFN and T-cell proliferation following antigen-specific stimulation. Furthermore, the antitumor efficacy of CAR.αPD1-T cells, CAR T cells, and CAR T cells combined with anti–PD-1 antibody was determined using a xenograft mouse model. Finally, the underlying mechanism was investigated by analyzing the expansion and functional capacity of TILs. Results: Human anti–PD-1 CPIs secreted by CAR.αPD1-T cells efficiently bound to PD-1 and reversed the inhibitory effect of PD-1/PD-L1 interaction on T-cell function. PD-1 blockade by continuously secreted anti–PD-1 attenuated the inhibitory T-cell signaling and enhanced T-cell expansion and effector function both in vitro and in vivo . In the xenograft mouse model, we demonstrated that the secretion of anti–PD-1 enhanced the antitumor activity of CAR T cells and prolonged overall survival. Conclusions: With constitutive anti–PD-1 secretion, CAR.αPD1-T cells are more functional and expandable, and more efficient at tumor eradication than parental CAR T cells. Collectively, our study presents an important and novel strategy that enables CAR T cells to achieve better antitumor immunity, especially in the treatment of solid tumors. Clin Cancer Res; 23(22); 6982–92. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 5
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    Transparent arrays of bilayer-nanomesh microelectrodes for simultaneous electrophysiology and two-photon imaging in the brain (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-09-06
    Description: Transparent microelectrode arrays have emerged as increasingly important tools for neuroscience by allowing simultaneous coupling of big and time-resolved electrophysiology data with optically measured, spatially and type resolved single neuron activity. Scaling down transparent electrodes to the length scale of a single neuron is challenging since conventional transparent conductors are limited by their capacitive electrode/electrolyte interface. In this study, we establish transparent microelectrode arrays with high performance, great biocompatibility, and comprehensive in vivo validations from a recently developed, bilayer-nanomesh material composite, where a metal layer and a low-impedance faradaic interfacial layer are stacked reliably together in a same transparent nanomesh pattern. Specifically, flexible arrays from 32 bilayer-nanomesh microelectrodes demonstrated near-unity yield with high uniformity, excellent biocompatibility, and great compatibility with state-of-the-art wireless recording and real-time artifact rejection system. The electrodes are highly scalable, with 130 kilohms at 1 kHz at 20 μm in diameter, comparable to the performance of microelectrodes in nontransparent Michigan arrays. The highly transparent, bilayer-nanomesh microelectrode arrays allowed in vivo two-photon imaging of single neurons in layer 2/3 of the visual cortex of awake mice, along with high-fidelity, simultaneous electrical recordings of visual-evoked activity, both in the multi-unit activity band and at lower frequencies by measuring the visual-evoked potential in the time domain. Together, these advances reveal the great potential of transparent arrays from bilayer-nanomesh microelectrodes for a broad range of utility in neuroscience and medical practices.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Superconducting cavity electro-optics: A platform for coherent photon conversion between superconducting and photonic circuits (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-08-18
    Description: Leveraging the quantum information-processing ability of superconducting circuits and long-distance distribution ability of optical photons promises the realization of complex and large-scale quantum networks. In such a scheme, a coherent and efficient quantum transducer between superconducting and photonic circuits is critical. However, this quantum transducer is still challenging because the use of intermediate excitations in current schemes introduces extra noise and limits bandwidth. We realize direct and coherent transduction between superconducting and photonic circuits based on the triple-resonance electro-optic principle, with integrated devices incorporating both superconducting and optical cavities on the same chip. Electromagnetically induced transparency is observed, indicating the coherent interaction between microwave and optical photons. Internal conversion efficiency of 25.9 ± 0.3% has been achieved, with 2.05 ± 0.04% total efficiency. Superconducting cavity electro-optics offers broad transduction bandwidth and high scalability and represents a significant step toward integrated hybrid quantum circuits and distributed quantum computation.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Analysis of the bystander effect in cone photoreceptors via a guided neural network platform (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-05-10
    Description: The mammalian retina system consists of a complicated photoreceptor structure, which exhibits extensive random synaptic connections. To study retinal development and degeneration, various experimental models have been used previously, but these models are often uncontrollable, are difficult to manipulate, and do not provide sufficient similarity or precision. Therefore, the mechanisms in many retinal diseases remain unclear because of the limited capability in observing the progression and molecular driving forces. For example, photoreceptor degeneration can spread to surrounding healthy photoreceptors via a phenomenon known as the bystander effect; however, no in-depth observations can be made to decipher the molecular mechanisms or the pathways that contribute to the spreading. It is then necessary to build dissociated neural networks to investigate the communications with controllability of cells and their treatment. We developed a neural network chip (NN-Chip) to load single neurons into highly ordered microwells connected by microchannels for synapse formation to build the neural network. By observing the distribution of apoptosis spreading from light-induced apoptotic cones to the surrounding cones, we demonstrated convincing evidence of the existence of a cone-to-cone bystander killing effect. Combining the NN-Chip with microinjection technology, we also found that the gap junction protein connexin 36 (Cx36) is critical for apoptosis spreading and the bystander effect in cones. In addition, our unique NN-Chip platform provides a quantitative, high-throughput tool for investigating signaling mechanisms and behaviors in neurons and opens a new avenue for screening potential drug targets to cure retinal diseases.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Multicomponent intermetallic nanoparticles and superb mechanical behaviors of complex alloys (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-11-23
    Description: Alloy design based on single–principal-element systems has approached its limit for performance enhancements. A substantial increase in strength up to gigapascal levels typically causes the premature failure of materials with reduced ductility. Here, we report a strategy to break this trade-off by controllably introducing high-density ductile multicomponent intermetallic nanoparticles (MCINPs) in complex alloy systems. Distinct from the intermetallic-induced embrittlement under conventional wisdom, such MCINP-strengthened alloys exhibit superior strengths of 1.5 gigapascals and ductility as high as 50% in tension at ambient temperature. The plastic instability, a major concern for high-strength materials, can be completely eliminated by generating a distinctive multistage work-hardening behavior, resulting from pronounced dislocation activities and deformation-induced microbands. This MCINP strategy offers a paradigm to develop next-generation materials for structural applications.
    Keywords: Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Autoregulation of Chk1 Phosphorylation (2012)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2012-08-03
    Description: Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, is centrally involved in cell-cycle checkpoints and cellular response to DNA damage. Phosphorylation of Chk1 at 2 Ser/Gln (SQ) sites, Ser-317 and Ser-345, by the upstream kinase ATR is critical for checkpoint activation. However, the precise molecular mechanisms controlling Chk1 phosphorylation and subsequent checkpoint activation are not well understood. Here, we report unique autoregulatory mechanisms that control protein phosphorylation of human Chk1, as well as checkpoint activation and cell viability. Phosphorylation of Ser-317 is required, but not sufficient, for maximal phosphorylation at Ser-345. The N-terminal kinase domain of Chk1 prevents Chk1 phosphorylation at the C-terminus by ATR in the absence of DNA damage. Loss of the inhibitory effect imposed by the N-terminus causes constitutive phosphorylation of Chk1 by ATR under normal growth conditions, which in turn triggers artificial checkpoints that suppress the S-phase progression. Furthermore, two point mutations were identified that rendered Chk1 constitutively active, and expression of the constitutively active mutant form of Chk1 inhibited cancer cell proliferation. Our findings therefore reveal unique regulatory mechanisms of Chk1 phosphorylation and suggest that expression of constitutively active Chk1 may represent a novel strategy to suppress tumor growth. Cancer Res; 72(15); 3786–94. ©2012 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 10
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    Hsp90{alpha} Levels in Lung Cancer (2014)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2014-12-02
    Description: Purpose: Altered expression of heat shock protein 90 alpha (Hsp90α) was associated with tumor development, progression, and metastasis. This study explored plasma levels of Hsp90α protein in patients with lung cancer and other controls to assess its diagnostic value and monitor treatment responses for patients with lung cancer. Experimental Design: A total of 2,247 individuals were recruited and assigned into two cohorts as static and dynamic groups. ELISA analysis and confirmation of plasma Hsp90α protein levels for association with tumor stages and treatment responses, respectively, were performed. Results: The average plasma levels of Hsp90α protein in patients with lung cancer were significantly higher than in healthy controls ( P 〈 0.0001). Plasma levels of Hsp90α protein in patients with advanced lung cancer (stage III–IV) were higher than in patients with early-stage lung cancer (stage I–II; P 〈 0.001). Using a cutoff value of 56.33 ng/mL to separate lung cancer from other controls, the sensitivity and specificity reached 72.18% (95% CI, 0.695–0.749) and 78.70% (95% CI, 0.761–0.813), respectively. To confirm the different levels in the second cohort, plasma levels of Hsp90α protein showed a statistically significant difference between preoperative and postoperative patients in surgical patient groups ( P 〈 0.007). There was also a statistically significant difference between the disease progressive group and stable disease group, with regard to partial response after chemotherapy ( P 〈 0.0001). Conclusions: This study demonstrated that plasma Hsp90α protein levels are useful as a diagnostic biomarker in lung cancer and predict the responses of patients with lung cancer to chemotherapy. Clin Cancer Res; 20(23); 6016–22. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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