Discovery and characterization of stereodefined PMO-gapmers targeting tau.

Antisense oligonucleotides (ASOs) are an important class of therapeutics to treat genetic diseases, and expansion of this modality to neurodegenerative disorders has been an active area of research. To realize chronic administration of ASO therapeutics to treat neurodegenerative diseases, new chemical modifications that improve activity and safety profiles are still needed. Furthermore, it is highly desirable to develop a single stereopure ASO with a defined activity and safety profile to avoid any efficacy and safety concerns due to the batch-to-batch variation in the composition of diastereomers.

Cautionary tales on the use of proxies to estimate body size and form of extinct animals.

Body size is of fundamental importance to our understanding of extinct organisms. Physiology, ecology and life history are all strongly influenced by body size and shape, which ultimately determine how a species interacts with its environment. Reconstruction of body size and form in extinct animals provides insight into the dynamics underlying community composition and faunal turnover in past ecosystems and broad macroevolutionary trends.

Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

A new cochliodont anterior tooth plate from the Mississippian of Alabama (USA) having implications for the origin of tooth plates from tooth files.

Background: Paleozoic holocephalian tooth plates are rarely found articulated in their original positions. When they are found isolated, it is difficult to associate the small, anterior tooth plates with the larger, more posterior ones. Tooth plates are presumed to have evolved from fusion of tooth files.

Computerized estimation of patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy.

We have developed a computerized method for estimating patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy. The patient setup errors were estimated based on a template-matching technique that compared the portal image and a localized pelvic template image with a clinical target volume produced from a digitally reconstructed radiography (DRR) image of each patient. We evaluated the proposed method by calculating the residual error between the patient setup error obtained by the proposed method and the gold standard setup error determined by consensus between two radiation oncologists.

Catalytic asymmetric synthesis of chiral tertiary organoboronic esters through conjugate boration of beta-substituted cyclic enones.

The first catalytic enantioselective conjugate boration of beta-substituted cyclic enones was developed to produce enantiomerically enriched tertiary organoboronates. The optimized asymmetric catalyst includes a QuinoxP*-CuO(t)Bu complex generated from CuPF(6)(CH(3)CN)(4) and LiO(t)Bu. In situ generated LiPF(6) significantly increased product yield.

Optimized dynamical decoupling in a model quantum memory.

Any quantum system, such as those used in quantum information or magnetic resonance, is subject to random phase errors that can dramatically affect the fidelity of a desired quantum operation or measurement. In the context of quantum information, quantum error correction techniques have been developed to correct these errors, but resource requirements are extraordinary. The realization of a physically tractable quantum information system will therefore be facilitated if qubit (quantum bit) error rates are far below the so-called fault-tolerance error threshold, predicted to be of the order of 10(-3)-10(-6).

Frequency ratio of Al+ and Hg+ single-ion optical clocks; metrology at the 17th decimal place.

Time has always had a special status in physics because of its fundamental role in specifying the regularities of nature and because of the extraordinary precision with which it can be measured. This precision enables tests of fundamental physics and cosmology, as well as practical applications such as satellite navigation. Recently, a regime of operation for atomic clocks based on optical transitions has become possible, promising even higher performance.

Direct comparison of two cold-atom-based optical frequency standards by using a femtosecond-laser comb.

With a fiber-broadened, femtosecond-laser frequency comb, the 76-THz interval between two laser-cooled optical frequency standards was measured with a statistical uncertainty of 2x10(-13) in 5 s , to our knowledge the best short-term instability thus far reported for an optical frequency measurement. One standard is based on the calcium intercombination line at 657 nm, and the other, on the mercury ion electric-quadrupole transition at 282 nm. By linking this measurement to the known Ca frequency, we report a new frequency value for the Hg(+) clock transition with an improvement in accuracy of ~10(5) compared with its best previous measurement.

Observation of the 1S0-->3P0 clock transition in 27Al+.

We report, for the first time, laser spectroscopy of the 1S0-->3P0 clock transition in 27Al+. A single aluminum ion and a single beryllium ion are simultaneously confined in a linear Paul trap, coupled by their mutual Coulomb repulsion. This coupling allows the beryllium ion to sympathetically cool the aluminum ion and also enables transfer of the aluminum's electronic state to the beryllium's hyperfine state, which can be measured with high fidelity.

Precision atomic spectroscopy for improved limits on variation of the fine structure constant and local position invariance.

We report tests of local position invariance and the variation of fundamental constants from measurements of the frequency ratio of the 282-nm 199Hg+ optical clock transition to the ground state hyperfine splitting in 133Cs. Analysis of the frequency ratio of the two clocks, extending over 6 yr at NIST, is used to place a limit on its fractional variation of <5.8x10(-6) per change in normalized solar gravitational potential.

Single-atom optical clock with high accuracy.

For the past 50 years, atomic standards based on the frequency of the cesium ground-state hyperfine transition have been the most accurate time pieces in the world. We now report a comparison between the cesium fountain standard NIST-F1, which has been evaluated with an inaccuracy of about 4 x 10(-16), and an optical frequency standard based on an ultraviolet transition in a single, laser-cooled mercury ion for which the fractional systematic frequency uncertainty was below 7.2 x 10(-17).

Microfabricated surface-electrode ion trap for scalable quantum information processing.

Individual laser-cooled 24Mg+ ions are confined in a linear Paul trap with a novel geometry where gold electrodes are located in a single plane and the ions are trapped 40 microm above this plane. The relatively simple trap design and fabrication procedure are important for large-scale quantum information processing (QIP) using ions. Measured ion motional frequencies are compared to simulations.

Erratum: External-Field Shifts of the (199)Hg(+) Optical Frequency Standard.

[This corrects the article on p. 829 in vol. 105.

Creation of a six-atom 'Schrödinger cat' state.

Among the classes of highly entangled states of multiple quantum systems, the so-called 'Schrödinger cat' states are particularly useful. Cat states are equal superpositions of two maximally different quantum states. They are a fundamental resource in fault-tolerant quantum computing and quantum communication, where they can enable protocols such as open-destination teleportation and secret sharing.

Long-lived qubit memory using atomic ions.

We demonstrate experimentally a robust quantum memory using a magnetic-field-independent hyperfine transition in 9Be+ atomic ion qubits at a magnetic field B approximately = 0.01194 T. We observe that the single physical qubit memory coherence time is greater than 10 s, an improvement of approximately 5 orders of magnitude from previous experiments with 9Be+.

Hyperfine coherence in the presence of spontaneous photon scattering.

The coherence of a hyperfine-state superposition of a trapped 9Be+ ion in the presence of off-resonant light is studied experimentally. It is shown that Rayleigh elastic scattering of photons that does not change state populations also does not affect coherence. We observe coherence times that exceed the average scattering time of 19 photons which is determined from measured Stark shifts.

Spectroscopy using quantum logic.

We present a general technique for precision spectroscopy of atoms that lack suitable transitions for efficient laser cooling, internal state preparation, and detection. In our implementation with trapped atomic ions, an auxiliary "logic" ion provides sympathetic laser cooling, state initialization, and detection for a simultaneously trapped "spectroscopy" ion. Detection is achieved by applying a mapping operation to each ion, which results in a coherent transfer of the spectroscopy ion's internal state onto the logic ion, where it is then measured with high efficiency.

Measurement of the (199)Hg+ 5d9 6s2 (2)D(5/2) electric quadrupole moment and a constraint on the quadrupole shift.

The electric-quadrupole moment of the (199)Hg+ 5d9 6s2 (2)D(5/2) state is measured to be theta(D,5/2) = -2.29(8) x 10(-40) C m2. This value was determined by measuring the frequency of the (199)Hg+ 5d10 6s (2)S(1/2) --> 5d9 6s2 (2)D(5/2) optical clock transition for different applied electric-field gradients.

Implementation of the semiclassical quantum Fourier transform in a scalable system.

We report the implementation of the semiclassical quantum Fourier transform in a system of three beryllium ion qubits (two-level quantum systems) confined in a segmented multizone trap. The quantum Fourier transform is the crucial final step in Shor's algorithm, and it acts on a register of qubits to determine the periodicity of the quantum state's amplitudes. Because only probability amplitudes are required for this task, a more efficient semiclassical version can be used, for which only single-qubit operations conditioned on measurement outcomes are required.

Enhanced quantum state detection efficiency through quantum information processing.

We investigate theoretically and experimentally how quantum state-detection efficiency is improved by the use of quantum information processing (QIP). Experimentally, we encode the state of one 9Be(+) ion qubit with one additional ancilla qubit. By measuring both qubits, we reduce the state-detection error in the presence of noise.

Realization of quantum error correction.

Scalable quantum computation and communication require error control to protect quantum information against unavoidable noise. Quantum error correction protects information stored in two-level quantum systems (qubits) by rectifying errors with operations conditioned on the measurement outcomes. Error-correction protocols have been implemented in nuclear magnetic resonance experiments, but the inherent limitations of this technique prevent its application to quantum information processing.

Quantum dense coding with atomic qubits.

We report the implementation of quantum dense coding on individual atomic qubits with the use of two trapped 9Be+ ions. The protocol is implemented with a complete Bell measurement that distinguishes the four operations used to encode two bits of classical information. We measure an average transmission fidelity of 0.

Deterministic quantum teleportation of atomic qubits.

Quantum teleportation provides a means to transport quantum information efficiently from one location to another, without the physical transfer of the associated quantum-information carrier. This is achieved by using the non-local correlations of previously distributed, entangled quantum bits (qubits). Teleportation is expected to play an integral role in quantum communication and quantum computation.

Toward Heisenberg-limited spectroscopy with multiparticle entangled states.

The precision in spectroscopy of any quantum system is fundamentally limited by the Heisenberg uncertainty relation for energy and time. For N systems, this limit requires that they be in a quantum-mechanically entangled state. We describe a scalable method of spectroscopy that can potentially take full advantage of entanglement to reach the Heisenberg limit and has the practical advantage that the spectroscopic information is transferred to states with optimal protection against readout noise.