Publications by authors named "Kenneth R Brown"

25 Publications

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Dipole-phonon quantum logic with alkaline-earth monoxide and monosulfide cations.

Phys Chem Chem Phys 2020 Nov 3;22(43):24964-24973. Epub 2020 Nov 3.

Department of Physics and Astronomy, University of California, Los Angeles, California 90095, USA. and Center for Quantum Science and Engineering, University of California, Los Angeles, California 90095, USA.

Dipole-phonon quantum logic (DPQL) leverages the interaction between polar molecular ions and the motional modes of a trapped-ion Coulomb crystal to provide a potentially scalable route to quantum information science. Here, we study a class of candidate molecular ions for DPQL, the cationic alkaline-earth monoxides and monosulfides, which possess suitable structure for DPQL and can be produced in existing atomic ion experiments with little additional complexity. We present calculations of DPQL operations for one of these molecules, CaO, and discuss progress towards experimental realization. We also further develop the theory of DPQL to include state preparation and measurement and entanglement of multiple molecular ions.
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http://dx.doi.org/10.1039/d0cp04574hDOI Listing
November 2020

High-Fidelity Two-Qubit Gates Using a Microelectromechanical-System-Based Beam Steering System for Individual Qubit Addressing.

Phys Rev Lett 2020 Oct;125(15):150505

Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708, USA.

In a large scale trapped atomic ion quantum computer, high-fidelity two-qubit gates need to be extended over all qubits with individual control. We realize and characterize high-fidelity two-qubit gates in a system with up to four ions using radial modes. The ions are individually addressed by two tightly focused beams steered using microelectromechanical system mirrors. We deduce a gate fidelity of 99.49(7)% in a two-ion chain and 99.30(6)% in a four-ion chain by applying a sequence of up to 21 two-qubit gates and measuring the final state fidelity. We characterize the residual errors and discuss methods to further improve the gate fidelity towards values that are compatible with fault-tolerant quantum computation.
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http://dx.doi.org/10.1103/PhysRevLett.125.150505DOI Listing
October 2020

Graphene reinforced carbon fibers.

Sci Adv 2020 Apr 24;6(17):eaaz4191. Epub 2020 Apr 24.

Department of Mechanical and Aerospace Engineering, University of Virginia, 122 Engineer's Way, Charlottesville, VA 22904, USA.

The superlative strength-to-weight ratio of carbon fibers (CFs) can substantially reduce vehicle weight and improve energy efficiency. However, most CFs are derived from costly polyacrylonitrile (PAN), which limits their widespread adoption in the automotive industry. Extensive efforts to produce CFs from low cost, alternative precursor materials have failed to yield a commercially viable product. Here, we revisit PAN to study its conversion chemistry and microstructure evolution, which might provide clues for the design of low-cost CFs. We demonstrate that a small amount of graphene can minimize porosity/defects and reinforce PAN-based CFs. Our experimental results show that 0.075 weight % graphene-reinforced PAN/graphene composite CFs exhibits 225% increase in strength and 184% enhancement in Young's modulus compared to PAN CFs. Atomistic ReaxFF and large-scale molecular dynamics simulations jointly elucidate the ability of graphene to modify the microstructure by promoting favorable edge chemistry and polymer chain alignment.
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http://dx.doi.org/10.1126/sciadv.aaz4191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182419PMC
April 2020

Photon-mediated charge exchange reactions between K atoms and Ca ions in a hybrid trap.

Phys Chem Chem Phys 2020 May 5;22(19):10870-10881. Epub 2020 May 5.

Department of Physics, Temple University, Philadelphia, Pennsylvania 19122, USA.

We present experimental evidence of charge exchange between laser-cooled potassium K atoms and calcium Ca ions in a hybrid atom-ion trap and give quantitative theoretical explanations for the observations. The K atoms and Ca ions are held in a magneto-optical (MOT) and a linear Paul trap, respectively. Fluorescence detection and high resolution time of flight mass spectra for both species are used to determine the remaining number of Ca ions, the increasing number of K ions, and K number density as functions of time. Simultaneous trap operation is guaranteed by alternating periods of MOT and Ca cooling lights, thus avoiding direct ionization of K by the Ca cooling light. We show that the K-Ca charge-exchange rate coefficient increases linearly from zero with K number density and the fraction of Ca ions in the 4p P electronically-excited state. Combined with our theoretical analysis, we conclude that these data can only be explained by a process that starts with a potassium atom in its electronic ground state and a calcium ion in its excited 4p P state producing ground-state K ions and metastable, neutral Ca (3d4p P) atoms, releasing only 150 cm equivalent relative kinetic energy. Charge-exchange between either ground- or excited-state K and ground-state Ca is negligibly small as no energetically-favorable product states are available. Our experimental and theoretical rate coefficients are in agreement given the uncertainty budgets.
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http://dx.doi.org/10.1039/d0cp01131bDOI Listing
May 2020

Stabilizer Slicing: Coherent Error Cancellations in Low-Density Parity-Check Stabilizer Codes.

Phys Rev Lett 2018 Dec;121(25):250502

Department of Physics, Duke University, Durham, North Carolina 27708, USA.

Coherent errors are a dominant noise process in many quantum computing architectures. Unlike stochastic errors, these errors can combine constructively and grow into highly detrimental overrotations. To combat this, we introduce a simple technique for suppressing systematic coherent errors in low-density parity-check stabilizer codes, which we call stabilizer slicing. The essential idea is to slice low-weight stabilizers into two equally weighted Pauli operators and then apply them by rotating in opposite directions, causing their overrotations to interfere destructively on the logical subspace. With access to native gates generated by three-body Hamiltonians, we can completely eliminate purely coherent overrotation errors, and for overrotation noise of 0.99 unitarity we achieve a 135-fold improvement in the logical error rate of surface-17. For more conventional two-body ion trap gates, we observe an 89-fold improvement for Bacon-Shor-13 with purely coherent errors which should be testable in near-term fault-tolerance experiments. This second scheme takes advantage of the prepared gauge degrees of freedom, and to our knowledge is the first example in which the state of the gauge directly affects the robustness of a code's memory. This Letter demonstrates that coherent noise is preferable to stochastic noise within certain code and gate implementations when the coherence is utilized effectively.
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http://dx.doi.org/10.1103/PhysRevLett.121.250502DOI Listing
December 2018

Quantum Error Correction Decoheres Noise.

Phys Rev Lett 2018 Nov;121(19):190501

Institute for Quantum Computing and Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.

Typical studies of quantum error correction assume probabilistic Pauli noise, largely because it is relatively easy to analyze and simulate. Consequently, the effective logical noise due to physically realistic coherent errors is relatively unknown. Here, we prove that encoding a system in a stabilizer code and measuring error syndromes decoheres errors, that is, causes coherent errors to converge toward probabilistic Pauli errors, even when no recovery operations are applied. Two practical consequences are that the error rate in a logical circuit is well quantified by the average gate fidelity at the logical level and that essentially optimal recovery operators can be determined by independently optimizing the logical fidelity of the effective noise per syndrome.
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http://dx.doi.org/10.1103/PhysRevLett.121.190501DOI Listing
November 2018

Spectroscopy of Molecular Ions in Coulomb Crystals.

J Phys Chem Lett 2018 Oct 21;9(19):5797-5804. Epub 2018 Sep 21.

School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332-0400 , United States.

In this Perspective, we examine the use of laser-cooled atomic ions and sympathetically cooled molecular ions in Coulomb crystals for molecular spectroscopy. Coulomb crystals are well-isolated environments that provide localization and long storage times for sensitive measurements of weak signals and cold temperatures for precise spectroscopy. Coulomb crystals of molecular and atomic ions enable the detection of single-photon molecular ion transitions at a range of wavelengths by a change in atomic ion fluorescence at visible wavelengths. We give an overview of the state of the art from action spectroscopy to quantum logic spectroscopy for a wide range of molecular transitions from rotational sublevels separated by 10 cm to rovibronic transitions at 25 000 cm. We emphasize how this system allows for unparalleled control of the molecular ion state for precision spectroscopy with applications in astrochemistry and fundamental physics. We conclude with an outlook of the use of this control in cold molecular ion reactions.
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http://dx.doi.org/10.1021/acs.jpclett.8b01387DOI Listing
October 2018

Rovibronic Spectroscopy of Sympathetically Cooled CaH.

J Phys Chem A 2018 Mar 16;122(12):3177-3181. Epub 2018 Mar 16.

Departments of Electrical and Computer Engineering and Chemistry , Duke University , Durham , North Carolina , United States.

We measure the rovibronic transitions X Σ, v″ = 0, J″ → A Σ, v' = 0-3, J' of CaH and obtain rotational constants for the A Σ state. The spectrum is obtained using two-photon photodissociation of CaH cotrapped with Doppler cooled Ca. The excitation is driven by a mode-locked, frequency-doubled Ti:Sapph laser, which is then pulse shaped to narrow the spectral bandwidth. The measured values of the rotational constants are in agreement with ab initio theory.
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http://dx.doi.org/10.1021/acs.jpca.7b12823DOI Listing
March 2018

Robust 2-Qubit Gates in a Linear Ion Crystal Using a Frequency-Modulated Driving Force.

Phys Rev Lett 2018 Jan;120(2):020501

School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.

In an ion trap quantum computer, collective motional modes are used to entangle two or more qubits in order to execute multiqubit logical gates. Any residual entanglement between the internal and motional states of the ions results in loss of fidelity, especially when there are many spectator ions in the crystal. We propose using a frequency-modulated driving force to minimize such errors. In simulation, we obtained an optimized frequency-modulated 2-qubit gate that can suppress errors to less than 0.01% and is robust against frequency drifts over ±1  kHz. Experimentally, we have obtained a 2-qubit gate fidelity of 98.3(4)%, a state-of-the-art result for 2-qubit gates with five ions.
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http://dx.doi.org/10.1103/PhysRevLett.120.020501DOI Listing
January 2018

Fault-tolerant quantum error detection.

Sci Adv 2017 10 20;3(10):e1701074. Epub 2017 Oct 20.

Joint Quantum Institute and Joint Center for Quantum Information and Computer Science, University of Maryland Department of Physics and National Institute of Standards and Technology, College Park, MD 20742, USA.

Quantum computers will eventually reach a size at which quantum error correction becomes imperative. Quantum information can be protected from qubit imperfections and flawed control operations by encoding a single logical qubit in multiple physical qubits. This redundancy allows the extraction of error syndromes and the subsequent detection or correction of errors without destroying the logical state itself through direct measurement. We show the encoding and syndrome measurement of a fault-tolerantly prepared logical qubit via an error detection protocol on four physical qubits, represented by trapped atomic ions. This demonstrates the robustness of a logical qubit to imperfections in the very operations used to encode it. The advantage persists in the face of large added error rates and experimental calibration errors.
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http://dx.doi.org/10.1126/sciadv.1701074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650489PMC
October 2017

Vibronic Spectroscopy of Sympathetically Cooled CaH.

Chemphyschem 2016 Nov 25;17(22):3764-3768. Epub 2016 Aug 25.

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

We report the measurement of the 1 Σ→2 Σ transition of CaH by resonance-enhanced photodissociation of CaH that is co-trapped with laser-cooled Ca . We observe four resonances that we assign to transitions from the vibrational v=0 ground state to the v'=1-4 excited states based on theoretical predictions. A simple theoretical model that assumes instantaneous dissociation after resonant excitation yields results in good agreement with the observed spectral features except for the unobserved v'=0 peak. This discrepancy is attributed to an insufficient understanding of the dissociation process, and further experimental and theoretical studies are required to confirm the assignment. The resolution of our experiment is limited by the mode-locked excitation laser, but this survey spectroscopy enables future rotationally resolved studies with applications in astrochemistry and precision measurement.
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http://dx.doi.org/10.1002/cphc.201600645DOI Listing
November 2016

Observation of vibrational overtones by single-molecule resonant photodissociation.

Nat Commun 2015 Jul 22;6:7825. Epub 2015 Jul 22.

Schools of Chemistry and Biochemistry, Computational Science and Engineering, and Physics, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, USA.

Molecular ions can be held in a chain of laser-cooled atomic ions by sympathetic cooling. This system is ideal for performing high-precision molecular spectroscopy with applications in astrochemistry and fundamental physics. Here we show that this same system can be coupled with a broadband laser to discover new molecular transitions. We use three-ion chains of Ca(+) and CaH(+) to observe vibrational transitions via resonance-enhanced multiphoton dissociation detected by Ca(+) fluorescence. On the basis of theoretical calculations, we assign the observed peaks to the transition from the ground vibrational state, ν=0 to ν=9 and 10. Our method allows us to track single-molecular events, and it can be extended to work with any molecule by using normal mode frequency shifts to detect the dissociation. This survey spectroscopy serves as a bridge to the precision spectroscopy required for molecular ion control.
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http://dx.doi.org/10.1038/ncomms8825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525170PMC
July 2015

Physics Probing the electron.

Authors:
Kenneth R Brown

Science 2014 Jan 19;343(6168):255-6. Epub 2013 Dec 19.

Schools of Chemistry and Biochemistry; Computational Science and Engineering; and Physics, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.

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http://dx.doi.org/10.1126/science.1246820DOI Listing
January 2014

Modular cryostat for ion trapping with surface-electrode ion traps.

Rev Sci Instrum 2013 Apr;84(4):043112

School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.

We present a simple cryostat purpose built for use with surface-electrode ion traps, designed around an affordable, large cooling power commercial pulse tube refrigerator. A modular vacuum enclosure with a single vacuum space facilitates interior access and enables rapid turnaround and flexibility for future modifications. Long rectangular windows provide nearly 360° of optical access in the plane of the ion trap, while a circular bottom window near the trap enables NA 0.4 light collection without the need for in-vacuum optics. We evaluate the system's mechanical and thermal characteristics and we quantify ion trapping performance by trapping (40)Ca(+), finding small stray electric fields, long ion lifetimes, and low ion heating rates.
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http://dx.doi.org/10.1063/1.4802948DOI Listing
April 2013

Identifying single molecular ions by resolved sideband measurements.

J Phys Chem A 2013 Oct 22;117(39):9725-31. Epub 2013 Apr 22.

Schools of Chemistry and Biochemistry; Computational Science and Engineering; and Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.

The masses of single molecular ions are nondestructively measured by cotrapping the ion of interest with a laser-cooled atomic ion, (40)Ca(+). Measurement of the resolved sidebands of a dipole forbidden transition on the atomic ion reveals the normal-mode frequencies of the two ion system. The mass of two molecular ions, (40)CaH(+) and (40)Ca(16)O(+), are then determined from the normal-mode frequencies. Isotopes of Ca(+) are used to determine the effects of stray electric fields on the normal mode measurement. The future use of resolved sideband experiments for molecular spectroscopy is also discussed.
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http://dx.doi.org/10.1021/jp312368aDOI Listing
October 2013

Quantum computing: chemistry from photons.

Authors:
Kenneth R Brown

Nat Chem 2010 Feb;2(2):76-7

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http://dx.doi.org/10.1038/nchem.527DOI Listing
February 2010

Suppression of heating rates in cryogenic surface-electrode ion traps.

Phys Rev Lett 2008 Jan 10;100(1):013001. Epub 2008 Jan 10.

Center for Ultracold Atoms, Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

Dense arrays of trapped ions provide one way of scaling up ion trap quantum information processing. However, miniaturization of ion traps is currently limited by sharply increasing motional state decoherence at sub-100 mum ion-electrode distances. We characterize heating rates in cryogenically cooled surface-electrode traps, with characteristic sizes in the 75 to 150 mum range. Upon cooling to 6 K, the measured rates are suppressed by 7 orders of magnitude, 2 orders of magnitude below previously published data of similarly sized traps operated at room temperature. The observed noise depends strongly on the fabrication process, which suggests further improvements are possible.
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http://dx.doi.org/10.1103/PhysRevLett.100.013001DOI Listing
January 2008

Condition-specific competition allows coexistence of competitively superior exotic oysters with native oysters.

J Anim Ecol 2008 Jan;77(1):5-15

Institute for Water & Environmental Resource Management & Department of Environmental Sciences, University of Technology Sydney, Broadway, NSW 2007 Australia.

1. Trade-offs between competitive ability and tolerance of abiotic stress are widespread in the literature. Thus, condition-specific competition may explain spatial variability in the success of some biological invaders and why, in environments where there is small-scale environmental variability, competitively inferior and superior species can coexist. 2. We tested the hypothesis that differences in abiotic stress alter the outcome of competitive interactions between the native Sydney rock oysters Saccostrea glomerata and exotic Pacific oysters Crassostrea gigas by experimentally testing patterns of intra- and interspecific competition across a tidal elevation gradient of abiotic stress at three sites on the east coast of Australia. 3. At low and mid-intertidal heights, exotic C. gigas were able to rapidly overgrow and smother native S. glomerata, which grew at c. 60% of the exotic's rate. In high intertidal areas, where C. gigas displayed about 80% mortality but similar growth rates to S. glomerata, the native oyster was not affected by the presence of the exotic species. 4. Asymmetrical effects of the exotic species on the native could not be replicated by manipulating densities of conspecifics, confirming that effects at low and mid-intertidal heights were due to interspecific competition. 5. Our results suggest that the more rapid growth of C. gigas than S. glomerata comes at the cost of higher mortality under conditions of abiotic stress. Thus, although C. gigas may rapidly overgrow S. glomerata at low and mid tidal heights, the native oyster will not be competitively excluded by the exotic due to release from competition at high intertidal elevations. 6. The success of trade-offs in explaining spatial variation in the outcome of competitive interactions between C. gigas and S. glomerata strengthen the claim that these may be a useful tool in the quest to produce general predictive models of invasion success.
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http://dx.doi.org/10.1111/j.1365-2656.2007.01316.xDOI Listing
January 2008

Compact, filtered diode laser system for precision spectroscopy.

Opt Lett 2007 Mar;32(5):572-4

Center for Ultracold Atoms, Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.

Stable, narrow-linewidth optical sources are necessary in modern atomic physics. An appealing approach to achieving approximately 10 kHz frequency stability is optical feedback. We have designed a compact external cavity diode laser with optical feedback to a filter cavity mounted on a single baseplate and enclosed inside a vacuum sealed box. The design was implemented for three wavelengths addressing the 422 nm cooling, 1091 nm repumping, and 674 nm clock transition lines of Sr(+). We are able to cool a single, trapped strontium ion to approximately 2 mK and observe motional sidebands of the 5S(1/2) <--> 4D(5/2) transition.
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http://dx.doi.org/10.1364/ol.32.000572DOI Listing
March 2007

Limitations of quantum simulation examined by simulating a pairing Hamiltonian using nuclear magnetic resonance.

Phys Rev Lett 2006 Aug 4;97(5):050504. Epub 2006 Aug 4.

Center for Bits and Atoms, Research Laboratory of Electronics, and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Quantum simulation uses a well-known quantum system to predict the behavior of another quantum system. Certain limitations in this technique arise, however, when applied to specific problems, as we demonstrate with a theoretical and experimental study of an algorithm proposed by Wu, Byrd, and Lidar [Phys. Rev. Lett. 89, 057904 (2002).10.1103/PhysRevLett.89.057904] to find the low-lying spectrum of a pairing Hamiltonian. While the number of elementary quantum gates required scales polynomially with the size of the system, it increases inversely to the desired error bound E. Making such simulations robust to decoherence using fault tolerance requires an additional factor of approximately 1/E gates. These constraints, along with the effects of control errors, are illustrated using a three qubit NMR system.
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http://dx.doi.org/10.1103/PhysRevLett.97.050504DOI Listing
August 2006

Heme O synthase and heme A synthase from Bacillus subtilis and Rhodobacter sphaeroides interact in Escherichia coli.

Biochemistry 2004 Oct;43(42):13541-8

Department of Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.

Cytochrome c oxidase requires multiple heme and copper cofactors to catalyze the reduction of molecular oxygen to water. Although significant progress has been made in understanding the transport and incorporation of the copper ions, considerably less is known about the trafficking and insertion of the heme cofactors. Heme O synthase (HOS) and heme A synthase (HAS) from Rhodobacter sphaeroides (Cox10 and Cox15, respectively) and Bacillus subtilis (CtaB and CtaA, respectively) have been cloned and expressed in Escherichia coli. Our results demonstrate that HOS copurifies with HAS and that HAS copurifies with HOS, indicating that HOS and HAS interact and may form a physiologically relevant complex in vivo. Consistent with this hypothesis, the presence of HAS alters the total level of farnesylated hemes, providing further evidence that HOS and HAS interact. Our current working model is that HOS and HAS form a complex and that heme O is transferred directly from HOS to HAS. Because of the strong sequence similarity and evolutionary relationship between R. sphaeroides and mitochondria, our data suggest that this complex may form in eukaryotes as well.
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http://dx.doi.org/10.1021/bi048469kDOI Listing
October 2004

Heme A synthase does not incorporate molecular oxygen into the formyl group of heme A.

Biochemistry 2004 Jul;43(27):8616-24

Department of Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.

Heme A is an obligatory cofactor in all eukaryotic and many prokaryotic cytochrome c oxidases. The final step in heme A biosynthesis requires the oxidation of the C8 methyl substituent on pyrrole ring D to an aldehyde, a reaction catalyzed by heme A synthase. To effect this transformation, heme A synthase is proposed to utilize a heme B cofactor, oxidizing the substrate via successive monooxygenase reactions. Consistent with this hypothesis, the activity of heme A synthase is found to be strictly dependent on molecular oxygen. Surprisingly, when cells expressing heme A synthase were incubated with (18)O(2), no significant incorporation of label was observed in heme A, the C8 alcohol intermediate, or the C8 overoxidized byproduct. Conversely, when the cells were grown in H(2)(18)O, partial labeling was observed at every heme oxygen position. These results suggest that the oxygen on the heme A aldehyde is derived from water. Although our data do not allow us to exclude the possibility of exchange with water inside of the cell, the results seem to question a mechanism utilizing successive monooxygenase reactions and support instead a mechanism of heme O oxidation via electron transfer.
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http://dx.doi.org/10.1021/bi049056mDOI Listing
July 2004

The antiparasitic moxidectin: safety, tolerability, and pharmacokinetics in humans.

J Clin Pharmacol 2003 Oct;43(10):1108-15

Experimental Medicine, Wyeth Research, 87 CambridgePark Drive, Cambridge, MA 02140, USA.

A study in healthy male volunteers was completed to evaluate the safety, tolerability, and pharmacokinetics of a single oral dose of the antiparasitic moxidectin (MOX). This drug is registered worldwide as a veterinary antiparasitic agent for use in companion and farm animals. This is the first study of MOX in humans. All subjects were between the ages of 18 and 45 years, with normal cardiac, hematologic, hepatic, and renal function. Doses of MOX studied were 3, 9, 18, and 36 mg in cohorts of 6 subjects each (5:1, MOX:placebo). At the 9-mg and 36-mg doses, two separate cohorts were completed, one in the fasted state and one after the consumption of a high-fat breakfast. For all other cohorts, administration was in the fasted state. Safety and tolerability were assessed by physical examinations, ongoing evaluation of adverse events (AEs), and measurement of laboratory values. Pharmacokinetic (PK) samples were collected just prior to dosing and at various time points until 80 days postdose. Safety assessments from all dose groups studied suggested that MOX was generally safe and well tolerated, with a slightly higher incidence of transient, mild, and moderate central nervous system AEs as the dose increased as compared to placebo. The PKs of MOX were dose proportional within the dose range studied, and the elimination half-life (t1/2 elim) was long (mean: 20.2-35.1 days). At the 9-mg and 36-mg doses, a high-fat breakfast was shown to delay and increase the overall absorption but did not increase maximal concentrations when compared to administration in the fasted state. In summary, the results from this study indicate that MOX is safe and well tolerated in humans between the doses of 3 mg and 36 mg.
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http://dx.doi.org/10.1177/0091270003257456DOI Listing
October 2003

Identification of novel hemes generated by heme A synthase: evidence for two successive monooxygenase reactions.

Biochemistry 2002 Sep;41(36):10906-13

Department of Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.

Heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase, is produced from heme B (protoheme) via two enzymatic reactions catalyzed by heme O synthase and heme A synthase. Heme O synthase is responsible for the addition of a farnesyl moiety, while heme A synthase catalyzes the oxidation of a methyl substituent to an aldehyde. We have cloned the heme O synthase and heme A synthase genes from Bacillus subtilis (ctaB and ctaA) and overexpressed them in Escherichia coli to probe the oxidative mechanism of heme A synthase. Because E. coli does not naturally produce or utilize heme A, this strategy effectively decoupled heme A biosynthesis from the native electron transfer pathway and heme A transport, allowing us to observe two previously unidentified hemes. We utilized HPLC, UV/visible spectroscopy, and tandem mass spectrometry to identify these novel hemes as derivatives of heme O containing an alcohol or a carboxylate moiety at position C8 on pyrrole ring D. We interpret these derivatives to be the putative alcohol intermediate and an overoxidized byproduct of heme A synthase. Because we have shown that all hemes produced by heme A synthase require O(2) for their synthesis, we propose that heme A synthase catalyzes the oxidation of the C8 methyl to an aldehyde group via two discrete monooxygenase reactions.
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http://dx.doi.org/10.1021/bi0203536DOI Listing
September 2002

Structures of the cuprous-thiolate clusters of the Mac1 and Ace1 transcriptional activators.

Biochemistry 2002 May;41(20):6469-76

University of Utah Health Sciences Center, 50 N. Medical Drive, 4C312, Salt Lake City, Utah 84132, USA.

X-ray absorption spectroscopy on the minimal copper-regulatory domains of the two copper-regulated transcription factors (Ace1 and Mac1) in Saccharomyces cerevisiae revealed the presence of a remarkably similar polycopper cluster in both proteins. The Cu-regulatory switch motif of Mac1 consisting of the C-terminal first Cys-rich motif, designated the C1 domain, binds four Cu(I) ions as does the Cu-regulatory domain of Ace1. The four Cu(I) ions are bound to each molecule in trigonal geometry. An extended X-ray absorption fine structure (EXAFS) arising from outer-shell Cu...Cu interactions at 2.7 and 2.9 A was apparent in each Cu(I) complex indicative of a polycopper cluster. The intensity of the 2.9 A Cu...Cu backscatter peak, apparently diminished by partial cancellation, dominates the EXAFS. The results suggest that CuAce1 and CuMac1(C1) contain somewhat distorted forms of a known [Cu(4)-S(6)] cage in which a core of Cu atoms forming an approximate tetrahedron is bound by bridging thiolates above each of the six edges. The tetracopper clusters bound by Ace1 and Mac1 differ in that the Ace1 cluster is coordinated entirely by cysteinyl thiolate, whereas the cysteine-deficient Mac1 cluster appears to consist of a Cu(4)(S-Cys)(5)(N-His) cluster with a bridging histidyl-derived nitrogen.
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http://dx.doi.org/10.1021/bi0160664DOI Listing
May 2002