Synthesis and Evaluation of Small Molecule Inhibitors of Pyruvate Carboxylase

Through structure-based drug design (SBDD), a series of small molecules have been synthesized and evaluated for inhibitory activity against the pyruvate carboxylase (PC) enzyme via two biological assays. The -hydroxycinnamic acid scaffold was identified as the most privileged scaffold for inhibition of PC. Analogues of phenylpyruvic acid were generated and evaluated, leading to the discovery of inhibitors with single digit micromolar (M) IC50 values. The most potent inhibitors identified were evaluated for inhibitory activity against other metalloproteins, and 2-hydroxy-3-(quinolone-2-yl)propenoic acid did not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase, or lactate dehydrogenase. The small molecules presented in this work represent the most potent inhibitors of the pyruvate carboxylase enzyme to date

Tracking the Feeding Patterns of Tsetse Flies (Glossina Genus) by Analysis of Bloodmeals Using Mitochondrial Cytochromes Genes

Tsetse flies are notoriously difficult to observe in nature, particularly when populations densities are low. It is therefore difficult to observe them on their hosts in nature; hence their vertebrate species can very often only be determined indirectly by analysis of their gut contents. This knowledge is a critical component of the information on which control tactics can be developed. The objective of this study was to determine the sources of tsetse bloodmeals, hence investigate their feeding preferences. We used mitochondrial cytochrome c oxidase 1 (COI) and cytochrome b (cytb) gene sequences for identification of tsetse fly blood meals, in order to provide a foundation for rational decisions to guide control of trypanosomiasis, and their vectors. Glossina swynnertoni were sampled from Serengeti (Tanzania) and G. pallidipes from Kenya (Nguruman and Busia), and Uganda. Sequences were used to query public databases, and the percentage identities obtained used to identify hosts. An initial assay showed that the feeds were from single sources. Hosts identified from blood fed flies collected in Serengeti ecosystem, included buffaloes (25/40), giraffes (8/40), warthogs (3/40), elephants (3/40) and one spotted hyena. In Nguruman, where G. pallidipes flies were analyzed, the feeds were from elephants (6/13) and warthogs (5/13), while buffaloes and baboons accounted for one bloodmeal each. Only cattle blood was detected in flies caught in Busia and Uganda. Out of four flies tested in Mbita Point, Suba District in western Kenya, one had fed on cattle, the other three on the Nile monitor lizard. These results demonstrate that cattle will form an integral part of a control strategy for trypanosomiasis in Busia and Uganda, while different approaches are required for Serengeti and Nguruman ecosystems, where wildlife abound and are the major component of the tsetse fly food source

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Resolving catastrophic error bursts from cosmic rays in large arrays of superconducting qubits

Scalable quantum computing can become a reality with error correction, provided coherent qubits can be constructed in large arrays. The key premise is that physical errors can remain both small and sufficiently uncorrelated as devices scale, so that logical error rates can be exponentially suppressed. However, energetic impacts from cosmic rays and latent radioactivity violate both of these assumptions. An impinging particle ionizes the substrate, radiating high energy phonons that induce a burst of quasiparticles, destroying qubit coherence throughout the device. High-energy radiation has been identified as a source of error in pilot superconducting quantum devices, but lacking a measurement technique able to resolve a single event in detail, the effect on large scale algorithms and error correction in particular remains an open question. Elucidating the physics involved requires operating large numbers of qubits at the same rapid timescales as in error correction, exposing the event's evolution in time and spread in space. Here, we directly observe high-energy rays impacting a large-scale quantum processor. We introduce a rapid space and time-multiplexed measurement method and identify large bursts of quasiparticles that simultaneously and severely limit the energy coherence of all qubits, causing chip-wide failure. We track the events from their initial localised impact to high error rates across the chip. Our results provide direct insights into the scale and dynamics of these damaging error bursts in large-scale devices, and highlight the necessity of mitigation to enable quantum computing to scale

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Readout of a quantum processor with high dynamic range Josephson parametric amplifiers

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure