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  • 1
    Publication Date: 2013-12-03
    Description: Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B cell neoplasms, but its mechanism of action is unknown. Using quantitative proteomics, we found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. IKZF1 and IKZF3 are essential transcription factors in multiple myeloma. A single amino acid substitution of IKZF3 conferred resistance to lenalidomide-induced degradation and rescued lenalidomide-induced inhibition of cell growth. Similarly, we found that lenalidomide-induced interleukin-2 production in T cells is due to depletion of IKZF1 and IKZF3. These findings reveal a previously unknown mechanism of action for a therapeutic agent: alteration of the activity of an E3 ubiquitin ligase, leading to selective degradation of specific targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077049/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077049/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kronke, Jan -- Udeshi, Namrata D -- Narla, Anupama -- Grauman, Peter -- Hurst, Slater N -- McConkey, Marie -- Svinkina, Tanya -- Heckl, Dirk -- Comer, Eamon -- Li, Xiaoyu -- Ciarlo, Christie -- Hartman, Emily -- Munshi, Nikhil -- Schenone, Monica -- Schreiber, Stuart L -- Carr, Steven A -- Ebert, Benjamin L -- P01 CA078378/CA/NCI NIH HHS/ -- P01 CA108631/CA/NCI NIH HHS/ -- P01 CA155258/CA/NCI NIH HHS/ -- P50 CA100707/CA/NCI NIH HHS/ -- R01 HL082945/HL/NHLBI NIH HHS/ -- R01HL082945/HL/NHLBI NIH HHS/ -- RL1- HG004671/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):301-5. doi: 10.1126/science.1244851. Epub 2013 Nov 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brigham and Women's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24292625" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; HEK293 Cells ; Humans ; Ikaros Transcription Factor/genetics/*metabolism ; Interleukin-2/biosynthesis ; Multiple Myeloma/*metabolism ; Proteolysis ; T-Lymphocytes/drug effects/metabolism ; Thalidomide/*analogs & derivatives/pharmacology ; Ubiquitination
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-03-04
    Description: Author(s): Y. Liu, S. Shankar, N. Ofek, M. Hatridge, A. Narla, K. M. Sliwa, L. Frunzio, R. J. Schoelkopf, and M. H. Devoret Error correction by feedback is crucial in quantum computation, and an experiment now shows that two such methods can be integrated in a nested feedback protocol to obtain the best properties of both. [Phys. Rev. X 6, 011022] Published Thu Mar 03, 2016
    Electronic ISSN: 2160-3308
    Topics: Physics
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  • 3
    Publication Date: 2012-11-09
    Description: Defects in the availability of haem substrates or the catalytic activity of the terminal enzyme in haem biosynthesis, ferrochelatase (Fech), impair haem synthesis and thus cause human congenital anaemias. The interdependent functions of regulators of mitochondrial homeostasis and enzymes responsible for haem synthesis are largely unknown. To investigate this we used zebrafish genetic screens and cloned mitochondrial ATPase inhibitory factor 1 (atpif1) from a zebrafish mutant with profound anaemia, pinotage (pnt (tq209)). Here we describe a direct mechanism establishing that Atpif1 regulates the catalytic efficiency of vertebrate Fech to synthesize haem. The loss of Atpif1 impairs haemoglobin synthesis in zebrafish, mouse and human haematopoietic models as a consequence of diminished Fech activity and elevated mitochondrial pH. To understand the relationship between mitochondrial pH, redox potential, [2Fe-2S] clusters and Fech activity, we used genetic complementation studies of Fech constructs with or without [2Fe-2S] clusters in pnt, as well as pharmacological agents modulating mitochondrial pH and redox potential. The presence of [2Fe-2S] cluster renders vertebrate Fech vulnerable to perturbations in Atpif1-regulated mitochondrial pH and redox potential. Therefore, Atpif1 deficiency reduces the efficiency of vertebrate Fech to synthesize haem, resulting in anaemia. The identification of mitochondrial Atpif1 as a regulator of haem synthesis advances our understanding of the mechanisms regulating mitochondrial haem homeostasis and red blood cell development. An ATPIF1 deficiency may contribute to important human diseases, such as congenital sideroblastic anaemias and mitochondriopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504625/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504625/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shah, Dhvanit I -- Takahashi-Makise, Naoko -- Cooney, Jeffrey D -- Li, Liangtao -- Schultz, Iman J -- Pierce, Eric L -- Narla, Anupama -- Seguin, Alexandra -- Hattangadi, Shilpa M -- Medlock, Amy E -- Langer, Nathaniel B -- Dailey, Tamara A -- Hurst, Slater N -- Faccenda, Danilo -- Wiwczar, Jessica M -- Heggers, Spencer K -- Vogin, Guillaume -- Chen, Wen -- Chen, Caiyong -- Campagna, Dean R -- Brugnara, Carlo -- Zhou, Yi -- Ebert, Benjamin L -- Danial, Nika N -- Fleming, Mark D -- Ward, Diane M -- Campanella, Michelangelo -- Dailey, Harry A -- Kaplan, Jerry -- Paw, Barry H -- K01 DK085217/DK/NIDDK NIH HHS/ -- P01 HL032262/HL/NHLBI NIH HHS/ -- P30 DK072437/DK/NIDDK NIH HHS/ -- R01 DK052380/DK/NIDDK NIH HHS/ -- R01 DK070838/DK/NIDDK NIH HHS/ -- R01 DK096051/DK/NIDDK NIH HHS/ -- R01 HL082945/HL/NHLBI NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 22;491(7425):608-12. doi: 10.1038/nature11536. Epub 2012 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23135403" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Sideroblastic/genetics/metabolism/pathology ; Animals ; Disease Models, Animal ; Erythroblasts/cytology/*metabolism ; *Erythropoiesis ; Ferrochelatase/metabolism ; Genetic Complementation Test ; Heme/*biosynthesis ; Humans ; Hydrogen-Ion Concentration ; Mice ; Mitochondria/*metabolism/pathology ; Mitochondrial Proteins/deficiency/genetics/*metabolism ; Oxidation-Reduction ; Proteins/genetics/*metabolism ; Zebrafish/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-11-26
    Description: Quantum error correction codes are designed to protect an arbitrary state of a multi-qubit register from decoherence-induced errors, but their implementation is an outstanding challenge in the development of large-scale quantum computers. The first step is to stabilize a non-equilibrium state of a simple quantum system, such as a quantum bit (qubit) or a cavity mode, in the presence of decoherence. This has recently been accomplished using measurement-based feedback schemes. The next step is to prepare and stabilize a state of a composite system. Here we demonstrate the stabilization of an entangled Bell state of a quantum register of two superconducting qubits for an arbitrary time. Our result is achieved using an autonomous feedback scheme that combines continuous drives along with a specifically engineered coupling between the two-qubit register and a dissipative reservoir. Similar autonomous feedback techniques have been used for qubit reset, single-qubit state stabilization, and the creation and stabilization of states of multipartite quantum systems. Unlike conventional, measurement-based schemes, the autonomous approach uses engineered dissipation to counteract decoherence, obviating the need for a complicated external feedback loop to correct errors. Instead, the feedback loop is built into the Hamiltonian such that the steady state of the system in the presence of drives and dissipation is a Bell state, an essential building block for quantum information processing. Such autonomous schemes, which are broadly applicable to a variety of physical systems, as demonstrated by the accompanying paper on trapped ion qubits, will be an essential tool for the implementation of quantum error correction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shankar, S -- Hatridge, M -- Leghtas, Z -- Sliwa, K M -- Narla, A -- Vool, U -- Girvin, S M -- Frunzio, L -- Mirrahimi, M -- Devoret, M H -- England -- Nature. 2013 Dec 19;504(7480):419-22. doi: 10.1038/nature12802. Epub 2013 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Physics and Physics, Yale University, New Haven, Connecticut 06520, USA. ; 1] Department of Applied Physics and Physics, Yale University, New Haven, Connecticut 06520, USA [2] INRIA Paris-Rocquencourt, Domaine de Voluceau, BP 105, 78153 Le Chesnay Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24270808" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-07-22
    Description: Quantum error correction is required for a practical quantum computer because of the fragile nature of quantum information. In quantum error correction, information is redundantly stored in a large quantum state space and one or more observables must be monitored to reveal the occurrence of an error, without disturbing the information encoded in an unknown quantum state. Such observables, typically multi-quantum-bit parities, must correspond to a special symmetry property inherent in the encoding scheme. Measurements of these observables, or error syndromes, must also be performed in a quantum non-demolition way (projecting without further perturbing the state) and more quickly than errors occur. Previously, quantum non-demolition measurements of quantum jumps between states of well-defined energy have been performed in systems such as trapped ions, electrons, cavity quantum electrodynamics, nitrogen-vacancy centres and superconducting quantum bits. So far, however, no fast and repeated monitoring of an error syndrome has been achieved. Here we track the quantum jumps of a possible error syndrome, namely the photon number parity of a microwave cavity, by mapping this property onto an ancilla quantum bit, whose only role is to facilitate quantum state manipulation and measurement. This quantity is just the error syndrome required in a recently proposed scheme for a hardware-efficient protected quantum memory using Schrodinger cat states (quantum superpositions of different coherent states of light) in a harmonic oscillator. We demonstrate the projective nature of this measurement onto a region of state space with well-defined parity by observing the collapse of a coherent state onto even or odd cat states. The measurement is fast compared with the cavity lifetime, has a high single-shot fidelity and has a 99.8 per cent probability per single measurement of leaving the parity unchanged. In combination with the deterministic encoding of quantum information in cat states realized earlier, the quantum non-demolition parity tracking that we demonstrate represents an important step towards implementing an active system that extends the lifetime of a quantum bit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, L -- Petrenko, A -- Leghtas, Z -- Vlastakis, B -- Kirchmair, G -- Sliwa, K M -- Narla, A -- Hatridge, M -- Shankar, S -- Blumoff, J -- Frunzio, L -- Mirrahimi, M -- Devoret, M H -- Schoelkopf, R J -- England -- Nature. 2014 Jul 24;511(7510):444-8. doi: 10.1038/nature13436. Epub 2014 Jul 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Departments of Applied Physics and Physics, Yale University, New Haven, Connecticut 06511, USA [2] Center for Quantum Information, Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing 100084, China (L.S.); Institut fur Experimentalphysik, Universitat Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria and Institut fur Quantenoptik und Quanteninformation, Osterreichische Akademie der Wissenschaften, Otto-Hittmair-Platz 1, A-6020 Innsbruck, Austria (G.K.). ; Departments of Applied Physics and Physics, Yale University, New Haven, Connecticut 06511, USA. ; 1] Departments of Applied Physics and Physics, Yale University, New Haven, Connecticut 06511, USA [2] INRIA Paris-Rocquencourt, Domaine de Voluceau, BP 105, 78153 Le Chesnay Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043007" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2015-02-24
    Description: Physical systems usually exhibit quantum behavior, such as superpositions and entanglement, only when they are sufficiently decoupled from a lossy environment. Paradoxically, a specially engineered interaction with the environment can become a resource for the generation and protection of quantum states. This notion can be generalized to the confinement of a system into a manifold of quantum states, consisting of all coherent superpositions of multiple stable steady states. We have confined the state of a superconducting resonator to the quantum manifold spanned by two coherent states of opposite phases and have observed a Schrodinger cat state spontaneously squeeze out of vacuum before decaying into a classical mixture. This experiment points toward robustly encoding quantum information in multidimensional steady-state manifolds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leghtas, Z -- Touzard, S -- Pop, I M -- Kou, A -- Vlastakis, B -- Petrenko, A -- Sliwa, K M -- Narla, A -- Shankar, S -- Hatridge, M J -- Reagor, M -- Frunzio, L -- Schoelkopf, R J -- Mirrahimi, M -- Devoret, M H -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):853-7. doi: 10.1126/science.aaa2085.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Physics, Yale University, New Haven, CT 06520, USA. zaki.leghtas@yale.edu. ; Department of Applied Physics, Yale University, New Haven, CT 06520, USA. ; Institut National de Recherche en Informatique et en Automatique (INRIA) Paris-Rocquencourt, Domaine de Voluceau, B.P. 105, 78153 Le Chesnay Cedex, France. Department of Applied Physics, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700514" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2018-05-17
    Description: Author(s): P. Campagne-Ibarcq, E. Zalys-Geller, A. Narla, S. Shankar, P. Reinhold, L. Burkhart, C. Axline, W. Pfaff, L. Frunzio, R. J. Schoelkopf, and M. H. Devoret Two superconducting transmon qubits one meter apart are deterministically entangled by transferring a microwave photon between them. [Phys. Rev. Lett. 120, 200501] Published Wed May 16, 2018
    Keywords: General Physics: Statistical and Quantum Mechanics, Quantum Information, etc.
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 8
    Publication Date: 2016-09-21
    Description: Author(s): U. Vool, S. Shankar, S. O. Mundhada, N. Ofek, A. Narla, K. Sliwa, E. Zalys-Geller, Y. Liu, L. Frunzio, R. J. Schoelkopf, S. M. Girvin, and M. H. Devoret The transverse component of a superconducting qubit is continuously measured for the first time, showing quantum jumps between its eigenstates. [Phys. Rev. Lett. 117, 133601] Published Mon Sep 19, 2016
    Keywords: Atomic, Molecular, and Optical Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 9
    Publication Date: 2014-06-13
    Description: Josephson junction parametric amplifiers are playing a crucial role in the readout chain in superconducting quantum information experiments. However, their integration with current 3D cavity implementations poses the problem of transitioning between waveguide, coax cables, and planar circuits. Moreover, Josephson amplifiers require auxiliary microwave components, like directional couplers and/or hybrids, that are sources of spurious losses and impedance mismatches that limit measurement efficiency and amplifier tunability. We have developed a wireless architecture for these parametric amplifiers that eliminates superfluous microwave components and interconnects. This greatly simplifies their assembly and integration into experiments. We present an experimental realization of such a device operating in the 9–11 GHz band with about 100 MHz of amplitude gain-bandwidth product, on par with devices mounted in conventional sample holders. The simpler impedance environment presented to the amplifier also results in increased amplifier tunability.
    Print ISSN: 0003-6951
    Electronic ISSN: 1077-3118
    Topics: Physics
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  • 10
    Publication Date: 2016-09-07
    Description: Author(s): A. Narla, S. Shankar, M. Hatridge, Z. Leghtas, K. M. Sliwa, E. Zalys-Geller, S. O. Mundhada, W. Pfaff, L. Frunzio, R. J. Schoelkopf, and M. H. Devoret Communication that relies on quantum carriers, like single photons, can achieve a level of privacy unattainable by classical communication methods. In a new experiment, single microwave photons are used as carriers of quantum information in a manner robust to loss. [Phys. Rev. X 6, 031036] Published Tue Sep 06, 2016
    Electronic ISSN: 2160-3308
    Topics: Physics
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