Correlated charge noise and relaxation errors in superconducting qubits.

The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low1. Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.

Detection-loophole-free test of quantum nonlocality, and applications.

We present a source of entangled photons that violates a Bell inequality free of the "fair-sampling" assumption, by over 7 standard deviations. This violation is the first reported experiment with photons to close the detection loophole, and we demonstrate enough "efficiency" overhead to eventually perform a fully loophole-free test of local realism. The entanglement quality is verified by maximally violating additional Bell tests, testing the upper limit of quantum correlations. Finally, we use the source to generate "device-independent" private quantum random numbers at rates over 4 orders of magnitude beyond previous experiments.

Phosphonomycin: structure and synthesis.

Synthesis and resolution of the antibiotic phosphonomycin are described. The structure is (-)(IR, 2S)-1,2-epoxypropylphosphonic acid.

Measurement of a superconducting qubit with a microwave photon counter.

Fast, high-fidelity measurement is a key ingredient for quantum error correction. Conventional approaches to the measurement of superconducting qubits, involving linear amplification of a microwave probe tone followed by heterodyne detection at room temperature, do not scale well to large system sizes. We introduce an approach to measurement based on a microwave photon counter demonstrating raw single-shot measurement fidelity of 92%. Moreover, the intrinsic damping of the photon counter is used to extract the energy released by the measurement process, allowing repeated high-fidelity quantum nondemolition measurements. Our scheme provides access to the classical outcome of projective quantum measurement at the millikelvin stage and could form the basis for a scalable quantum-to-classical interface.

3-Cyanocephems, and carbon-3 heterocyclic-substituted cephems via 1,3-dipolar cycloadditions.

The transformation is described of 3-formylcephem 1 into its oxime, substituted oximes, and substituted hydrazones and, thence, into the 3-cyano, 3-diazomethyl, and 3-oxonitrilomethyl derivatives. These reactive 1,3-dipoles undergo 1,3-dipolar cycloadditions with various dipolarophiles to give C-3 heterocyclic-substituted cephems.

Synthesis and structure-activity relationships of peptidyl alpha-keto heterocycles as novel inhibitors of prolyl endopeptidase.

The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp2 nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.

Total syntheses of (+/-)-1-carbacefoxitin and -cefamandole and (+/-)-1-oxacefamandole.

The total syntheses of the (+/-)-1-carba analogues of cefoxitin (11), 7 alpha-methoxydeacetylcephalothin (5) and cefamandole (31) and the (+/-)-1-oxa analogue of cefamandole (43) are described. Their bioactivity spectra against 14 typical organisms are similar to those of their natural 1-thia counterparts, with the 1-carba compounds somewhat less active and the 1-oxa compound more active than the natural ones.

Structure-activity relationships in the 2-arylcarbapenem series: synthesis of 1-methyl-2-arylcarbapenems.

The labile tert-butyldimethylsilyl esters of the azetidinones 6-8b served as the crucial synthons in the preparation of the potentially useful ylide pyridyl thio esters 18-20. These intermediates were utilized to synthesize a host of title carbapenems 25-30d, 32, and 49-53. The antimicrobial properties and DHP-I susceptibility of these carbapenems were studied with reference to thienamycin.

The synthesis of 2-(functionalized methyl)-1 beta-methylcarbapenems.

The synthesis of 1 beta-methylcarbapenems having a ROCH2 substituent at the 2-position is described. Their in vitro antibacterial activity and DHP-I susceptibilities are presented.

Synthesis and antibacterial activity of novel 2-methyl-1-oxacephalosporins.

New 2-methyl-1-oxacephem compounds having 2-(2-aminothiazol-4-yl)-2-(alkoxyimino)acetamido substituents at C-7 and various C-3 side chains were synthesized starting from (3R,4S)-phenyloxazolinoazetidinone (8). Introduction of the 2 beta-methyl group into the 1-oxacephem nucleus increased the stability to beta-lactamases. OCP-9-176 (7b) having the (1-methylpyridinium-4-yl)thiomethyl group at C-3 showed potent antibacterial activity and a broad spectrum.

Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against methicillin-resistant Staphylococcus aureus.

A systematic approach toward building activity against methicillin-resistant staphylococci into the cephalosporin class of beta-lactam antibiotics is described. Initial work focused on finding the optimal linkage between the cephem nucleus and a biphenyl pharmacophore, which established that a thio linkage afforded potent activity in vitro. Efforts to optimize this activity by altering substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which although highly potent against MRSA, was also highly bound to serum proteins. Further work to decrease serum protein binding showed that replacement of the iodo substituent by the positively-charged isothiouronium group afforded potent activity and reduced serum binding, but insufficient aqueous solubility. Solubility was enhanced by incorporation of a second positively-charged group into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked sufficient stability to staphylococcal beta-lactamase enzymes. The second positive charge was incorporated into the cephem 3-substituent in order to utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7-substituents. These efforts culminated with the discovery of bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable with respect to potency against MRSA, serum binding, aqueous solubility, and beta-lactamase stability.

The design of new drugs that resist microbial inactivation.

Several possible strategems for overcoming the development of bacterial resistance are discussed. The design of new drugs that resist microbial inactivation is reviewed, with particular emphasis on the aminoglycoside and beta-lactam antibiotics. Examples of alteration of the inactivation site, decreased enzyme affinity, steric hindrance of enzymic inactivation, and semiempirical systematic modification of the parent antibiotic are presented. The role of the 7-alpha-methoxy group in cefoxitin and the cephamycins in conferring stability in the presence of beta-lactamase is best rationalized by its steric bulk. The effects of other 7-alpha-substituents are also discussed.

A stereocontrolled, enantiomerically specific total synthesis of thienamycin.

A versatile stereocontrolled total synthesis of thienamycin starting from L-aspartic acid is reported. Stereocontrol is achieved by potassium tri-sec-butylborohydride reduction of a thermodynamically formed 3 alpha-acetylazetidinone intermediate. The key [3.2.0] bicyclic ring system is prepared by a metal catalyzed carbene insertion reaction.