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"Wang, H"
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miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth
in vitro
and
in vivo
. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Journal Article
How China became capitalist
\"How China Became Capitalist details the extraordinary, and often accidental, journey that China has taken over the past thirty years in transforming itself from a closed agrarian socialist economy to an indomitable force in the international arena. The authors revitalize the debate around the development of the Chinese system through the use of primary sources. They persuasively argue that the reforms implemented by the Chinese leaders did not represent a concerted attempt to create a capitalist economy, but that the ideas from the West eventually culminated in a fundamental change to their socialist model, forming an accidental path to capitalism. Coase and Wang argue that the pragmatic approach of \"seeking truth from fact\" is in fact much more in line with Chinese culture. How China Became Capitalist challenges the received wisdom about the future of the Chinese economy, arguing that while China has enormous potential for growth, this could be hampered by the leaders' propensity for control, both in terms of economics and their monopoly of ideas and power\"-- Provided by publisher.
Book
Genome-wide prediction of disease variant effects with a deep protein language model
Predicting the effects of coding variants is a major challenge. While recent deep-learning models have improved variant effect prediction accuracy, they cannot analyze all coding variants due to dependency on close homologs or software limitations. Here we developed a workflow using ESM1b, a 650-million-parameter protein language model, to predict all ~450 million possible missense variant effects in the human genome, and made all predictions available on a web portal. ESM1b outperformed existing methods in classifying ~150,000 ClinVar/HGMD missense variants as pathogenic or benign and predicting measurements across 28 deep mutational scan datasets. We further annotated ~2 million variants as damaging only in specific protein isoforms, demonstrating the importance of considering all isoforms when predicting variant effects. Our approach also generalizes to more complex coding variants such as in-frame indels and stop-gains. Together, these results establish protein language models as an effective, accurate and general approach to predicting variant effects.
A modified framework leveraging a protein language model (ESM1b) is used to predict all possible 450 million missense variant effects in the human genome and shows potential for generalizing to more complex genetic variations such as indels and stop-gains.
Journal Article
The Taiwan voter
\"The Taiwan Voter examines the critical role ethnic and national identities play in politics, utilizing the case of Taiwan. Although elections there often raise international tensions, and have led to military demonstrations by China, no scholarly books have examined how Taiwan's voters make electoral choices in a dangerous environment. Critiquing the conventional interpretation of politics as an ideological battle between liberals and conservatives, The Taiwan Voter demonstrates in Taiwan the party system and voters' responses are shaped by one powerful determinant of national identity--the China factor. Taiwan's electoral politics draws international scholarly interest because of the prominent role of ethnic and national identification. While in most countries the many tangled strands of competing identities are daunting for scholarly analysis, in Taiwan the cleavages are powerful and limited in number, so the logic of interrelationships among issues, partisanship, and identity are particularly clear. The Taiwan Voter unites experts to investigate the ways in which social identities, policy views, and partisan preferences intersect and influence each other.These novel findings have wide applicability to other countries, and will be of interest to a broad range of social scientists interested in identity politics\"-- Provided by publisher.
Book
Taming harmful bursts and heat flux in high-confinement tokamak plasmas
A major challenge in tokamak fusion research is first-wall erosion caused by steady heat loads and sudden energy bursts known as edge-localized modes. Divertor detachment reduces steady-state heat flux, while resonant magnetic perturbations can suppress these instabilities. However, integrating the two has been difficult because they require conflicting operating conditions. Here we demonstrate simultaneous achievement of resonant magnetic perturbations mitigated small edge-localized modes and impurity seeded partial divertor detachment in plasmas with an ITER-similar shape on the DIII-D tokamak. Experiments and simulations show that resonant magnetic perturbations facilitate detachment by redistributing particles, lowering the core density and increasing the scrape-off layer density, thereby reducing the amount of injected gas required. Cooling-gas injection eliminates the secondary heat-flux peak created by three-dimensional magnetic lobes, while edge cooling weakens the plasma response to the applied magnetic fields. These advances illustrate a viable pathway for integrating edge stability control with power exhaust in future fusion reactors.
Tokamak walls suffer erosion from steady and bursty heat loads. Here, the authors demonstrate that optimizing 3D magnetic field and cooling gas injection can tame destructive plasma bursts while enabling cooler, safer exhaust conditions.
Journal Article
China and the West : McMaster and Pillsbury vs. Mahbubani and Wang
\"Increasingly in the West, China is being characterized as a threat to the liberal international order, one that must be overcome through economic, political, technological, and even military means. For those who believe that the policies of the Chinese Communist Party pose a threat to free and open societies, the U.S. and like-minded nations must band together to preserve a rules-based international order. For others, this approach spells disaster; it ignores the history and dynamics propelling China's rise to superpower status. Rather than threatening the post-war order, China is its best, and maybe only, guarantor in an era of declining U.S. leadership, increased regional instability, and slowing global growth. The twenty-fourth semi-annual Munk Debate, held on May 9, 2019, pits former Assistant to the President for National Security Affairs H.R. McMaster and Director for Chinese Strategy at the D.C.-based Hudson Institute think tank Michael Pillsbury against former President of the United Nations Security Council Kishore Mahbubani and president of one of China's top independent think tanks, the Center for China Globalization, Huiyao Wang to debate the threat of China to the liberal international order.\"-- Provided by publisher.
Book
Hierarchically buckled sheath-core fibers for superelastic electronics, sensors, and muscles
Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.
Journal Article
Generation of multicomponent atomic Schrödinger cat states of up to 20 qubits
Multipartite entangled states are crucial for numerous applications in quantum information science. However, the generation and verification of multipartite entanglement on fully controllable and scalable quantum platforms remains an outstanding challenge. We report the deterministic generation of an 18-qubit Greenberger-Horne-Zeilinger (GHZ) state and multicomponent atomic Schrödinger cat states of up to 20 qubits on a quantum processor, which features 20 superconducting qubits, also referred to as artificial atoms, interconnected by a bus resonator. By engineering a one-axis twisting Hamiltonian, the system of qubits, once initialized, coherently evolves to multicomponent atomic Schrödinger cat states—that is, superpositions of atomic coherent states including the GHZ state—at specific time intervals as expected. Our approach on a solid-state platform should not only stimulate interest in exploring the fundamental physics of quantum many-body systems, but also enable the development of applications in practical quantum metrology and quantum information processing.
Journal Article