Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase

We identified an autosomal recessive infantile-onset symptomatic epilepsy syndrome associated with developmental stagnation and blindness. Assuming a founder effect in a large Old Order Amish pedigree, we carried out a genome-wide screen for linkage and identified a single region of homozygosity on chromosome 2p12-p11.2 spanning 5.1 cM (maximum lod score of 6.84). We sequenced genes in the region and identified a nonsense mutation in SIAT9, which is predicted to result in the premature termination of the GM3 synthase enzyme (also called lactosylceramide alpha-2,3 sialyltransferase). GM3 synthase is a member of the sialyltransferase family and catalyzes the initial step in the biosynthesis of most complex gangliosides from lactosylceramide. Biochemical analysis of plasma glycosphingolipids confirmed that affected individuals lack GM3 synthase activity, as marked by a complete lack of GM3 ganglioside and its biosynthetic derivatives and an increase in lactosylceramide and its alternative derivatives. Although the relationship between defects in ganglioside catabolism and a range of lysosomal storage diseases is well documented, this is the first report, to our knowledge, of a disruption of ganglioside biosynthesis associated with human disease.     

Demonstration of an all-optical quantum controlled-NOT gate

The promise of tremendous computational power, coupled with the development of robust error-correcting schemes, has fuelled extensive efforts to build a quantum computer. The requirements for realizing such a device are confounding: scalable quantum bits (two-level quantum systems, or qubits) that can be well isolated from the environment, but also initialized, measured and made to undergo controllable interactions to implement a universal set of quantum logic gates. The usual set consists of single qubit rotations and a controlled-NOT (CNOT) gate, which flips the state of a target qubit conditional on the control qubit being in the state 1. Here we report an unambiguous experimental demonstration and comprehensive characterization of quantum CNOT operation in an optical system. We produce all four entangled Bell states as a function of only the input qubits' logical values, for a single operating condition of the gate. The gate is probabilistic (the qubits are destroyed upon failure), but with the addition of linear optical quantum non-demolition measurements, it is equivalent to the CNOT gate required for scalable all-optical quantum computation.     

Entanglement-free Heisenberg-limited phase estimation

Measurement underpins all quantitative science. A key example is the measurement of optical phase, used in length metrology and many other applications. Advances in precision measurement have consistently led to important scientific discoveries. At the fundamental level, measurement precision is limited by the number N of quantum resources (such as photons) that are used. Standard measurement schemes, using each resource independently, lead to a phase uncertainty that scales as 1/square root N-known as the standard quantum limit. However, it has long been conjectured that it should be possible to achieve a precision limited only by the Heisenberg uncertainty principle, dramatically improving the scaling to 1/N (ref. 3). It is commonly thought that achieving this improvement requires the use of exotic quantum entangled states, such as the NOON state. These states are extremely difficult to generate. Measurement schemes with counted photons or ions have been performed with N < or = 6 (refs 6-15), but few have surpassed the standard quantum limit and none have shown Heisenberg-limited scaling. Here we demonstrate experimentally a Heisenberg-limited phase estimation procedure. We replace entangled input states with multiple applications of the phase shift on unentangled single-photon states. We generalize Kitaev's phase estimation algorithm using adaptive measurement theory to achieve a standard deviation scaling at the Heisenberg limit. For the largest number of resources used (N = 378), we estimate an unknown phase with a variance more than 10 dB below the standard quantum limit; achieving this variance would require more than 4,000 resources using standard interferometry. Our results represent a drastic reduction in the complexity of achieving quantum-enhanced measurement precision.